Associations of neighborhood built, safety, and social environment with walking to and from school among elementary school-aged children in Chiba, Japan.

BACKGROUND: Although it is globally known that Japan has high prevalence of active school travel among children, there are few international studies on Japanese children's school travel. Moreover, only few studies have focused on the differences in their mode of travel between to-school and from-school. This study examined the associations of neighborhood built, safety, and social environments with walking to/from school among elementary school-aged children in Chiba, Japan. METHODS: We conducted an online survey with 1545 parents of children aged 6-12 years residing in Chiba between 25 and 27 November 2020 during the COVID-19 pandemic. A neighborhood was defined as the area of a postcode provided by the participants. Each neighborhood environment was assessed based on the built environment (new town designation, walkability, distance to school, population density), social environment (neighborhood cohesion and connection), and safety (CCTVs, a road section for walking alone, safety volunteers). Neighborhood walkability was measured using subscales of the Neighborhood Environment Walkability Scale (youth and abbreviated versions) including crime safety and traffic safety. Parents' perceived influence of COVID-19 on school commuting and after-school activities were also included in the model as covariates. Walking to and from school were separately analyzed using multinomial logistic regressions, where new towns and walkability were computed separately as explanatory variables. RESULTS: Four fifths of children walked to and from school daily. Walking to school was positively associated with crime safety, neighborhood connections, and schools sited in new towns. Walking from school had positive associations with traffic safety, neighborhood cohesion, and CCTVs, but negative associations with safety volunteers and after-school activities. The presence of a section for walking alone and perceived influence of COVID-19 had negative associations with walking to and from school. CONCLUSIONS: Recent social changes such as declining birthrate, decline in public elementary schools, and increasing after-school activities may change parental attitudes toward children's walking to/from school, and subsequently, their mode of school travel over time. To maintain the high prevalence of walking to/from school in Japan, multidisciplinary approaches involving different stakeholders from education, public health, and urban planning are required to overcome sectionalism and support this behavior in the long term.

Deep Neural Network for Reducing the Screening Workload in Systematic Reviews for Clinical Guidelines: Algorithm Validation Study.

BACKGROUND: Performing systematic reviews is a time-consuming and resource-intensive process. OBJECTIVE: We investigated whether a machine learning system could perform systematic reviews more efficiently. METHODS: All systematic reviews and meta-analyses of interventional randomized controlled trials cited in recent clinical guidelines from the American Diabetes Association, American College of Cardiology, American Heart Association (2 guidelines), and American Stroke Association were assessed. After reproducing the primary screening data set according to the published search strategy of each, we extracted correct articles (those actually reviewed) and incorrect articles (those not reviewed) from the data set. These 2 sets of articles were used to train a neural network-based artificial intelligence engine (Concept Encoder, Fronteo Inc). The primary endpoint was work saved over sampling at 95% recall (WSS@95%). RESULTS: Among 145 candidate reviews of randomized controlled trials, 8 reviews fulfilled the inclusion criteria. For these 8 reviews, the machine learning system significantly reduced the literature screening workload by at least 6-fold versus that of manual screening based on WSS@95%. When machine learning was initiated using 2 correct articles that were randomly selected by a researcher, a 10-fold reduction in workload was achieved versus that of manual screening based on the WSS@95% value, with high sensitivity for eligible studies. The area under the receiver operating characteristic curve increased dramatically every time the algorithm learned a correct article. CONCLUSIONS: Concept Encoder achieved a 10-fold reduction of the screening workload for systematic review after learning from 2 randomly selected studies on the target topic. However, few meta-analyses of randomized controlled trials were included. Concept Encoder could facilitate the acquisition of evidence for clinical guidelines.

Step Counts of Middle-Aged and Elderly Adults for 10 Months Before and After the Release of Pokémon GO in Yokohama, Japan.

BACKGROUND: Smartphones have been integrated into our society and are expected to serve as tools to improve health outcomes. In the summer of 2016, Pokémon GO, a location-based augmented reality game for smartphones was released; it attracted attention from the perspective of health, especially with its potential to increase physical activity (PA). A few studies have compared objectively measured step counts before and after the release of the game; however, they were conducted over a short study period and evaluated only young people. OBJECTIVE: The objective of this study was to confirm whether there was a difference in step counts between middle-aged and elderly players and nonplayers before and after the release of Pokémon GO. METHODS: A total of 46 players and 184 nonplayers aged ≥40 years were matched for sex, age group, and PA level; they were respondents to a questionnaire randomly sent to citizens who were given free pedometers by Yokohama city. Their play status was identified through the questionnaire. To investigate the change in step counts before and after the release of Pokémon GO according to play status, a 2-way repeated-measures analysis of variance was performed. Step counts 1 month before the release of the game were compared with those 8 months after the release. In addition, subgroup analyses according to sex, age group, PA level, and subjective health status were performed. RESULTS: The mean ages of players and nonplayers were 56.5 (SD 9.9) years and 57.3 (SD 9.6) years, respectively, and the mean baseline step counts of players and nonplayers were 7641.8 (SD 2754.5) and 7903.3 (SD 2674.7), respectively. There was no significant difference in the age and baseline step counts according to a t test (2-tailed). In the analysis of all samples, the interaction between play status and time effect was significant for 3 of 8 months after release. In the subgroup analyses, the interaction was significant for 3 months in men, 7 months in the 55-64-year-old group, 2 months in workers, 4 months in the active group in PA level, and 2 months in participants with subjectively good health. The interaction was significant for only 1 month, at most, in other subgroups. CONCLUSIONS: The present study confirmed a difference in step counts between players and nonplayers before and after the release of Pokémon GO. According to our analysis, step counts were higher until 7 months after the release. The player group maintained their step counts in winter, despite the decrease in step counts of nonplayers. In subgroup analyses, players were more likely to be men, aged <55 years, workers, active, and subjectively in good health.

CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites.

UNLABELLED: CRISPRdirect is a simple and functional web server for selecting rational CRISPR/Cas targets from an input sequence. The CRISPR/Cas system is a promising technique for genome engineering which allows target-specific cleavage of genomic DNA guided by Cas9 nuclease in complex with a guide RNA (gRNA), that complementarily binds to a ∼ 20 nt targeted sequence. The target sequence requirements are twofold. First, the 5'-NGG protospacer adjacent motif (PAM) sequence must be located adjacent to the target sequence. Second, the target sequence should be specific within the entire genome in order to avoid off-target editing. CRISPRdirect enables users to easily select rational target sequences with minimized off-target sites by performing exhaustive searches against genomic sequences. The server currently incorporates the genomic sequences of human, mouse, rat, marmoset, pig, chicken, frog, zebrafish, Ciona, fruit fly, silkworm, Caenorhabditis elegans, Arabidopsis, rice, Sorghum and budding yeast. AVAILABILITY: Freely available at http://crispr.dbcls.jp/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A-to-I editing in the miRNA seed region regulates target mRNA selection and silencing efficiency.

Hydrolytic deamination of adenosine to inosine (A-to-I) by adenosine deaminases acting on RNA (ADARs) is a post-transcriptional modification which results in a discrepancy between genomic DNA and the transcribed RNA sequence, thus contributing to the diversity of the transcriptome. Inosine preferentially base pairs with cytidine, meaning that A-to-I modifications in the mRNA sequences may be observed as A-to-G substitutions by the protein-coding machinery. Genome-wide studies have revealed that the majority of editing events occur in non-coding RNA sequences, but little is known about their functional meaning. MiRNAs are small non-coding RNAs that regulate the expression of target mRNAs with complementarities to their seed region. Here, we confirm that A-to-I editing in the miRNA seed duplex globally reassigns their target mRNAs in vivo, and reveal that miRNA containing inosine in the seed region exhibits a different degree of silencing efficiency compared to the corresponding miRNA with guanosine at the same position. The difference in base-pairing stability, deduced by melting temperature measurements, between seed-target duplexes containing either C:G or I:C pairs may account for the observed silencing efficiency. These findings unequivocally show that C:G and I:C pairs are biologically different in terms of gene expression regulation by miRNAs.

Downregulation of Nipah virus N mRNA occurs through interaction between its 3' untranslated region and hnRNP D.

Nipah virus (NiV) is a nonsegmented, single-stranded, negative-sense RNA virus belonging to the genus Henipavirus, family Paramyxoviridae. NiV causes acute encephalitis and respiratory disease in humans, is associated with high mortality, and poses a threat in southern Asia. The genomes of henipaviruses are about 18,246 nucleotides (nt) long, which is longer than those of other paramyxoviruses (around 15,384 nt). This difference is caused by the noncoding RNA region, particularly the 3' untranslated region (UTR), which occupies more than half of the noncoding RNA region. To determine the function(s) of the NiV noncoding RNA region, we investigated the effects of NiV 3' UTRs on reporter gene expression. The NiV N 3' UTR (nt 1 to 100) demonstrated strong repressor activity associated with hnRNP D protein binding to that region. Mutation of the hnRNP D binding site or knockdown of hnRNP D resulted in increased expression of the NiV N 3' UTR reporter. Our findings suggest that NiV N expression is repressed by hnRNP D through the NiV N 3' UTR and demonstrate the involvement of posttranscriptional regulation in the NiV life cycle. To the best of our knowledge, this provides the first report of the functions of the NiV noncoding RNA region.

[Commute mode - physical activity and the possibility of change to active commuting among Japanese workers: a descriptive study by region].

OBJECTIVES: Changing the mode of commuting from nonactive by car or motorcycle to active by walking, cycling, or public transport is expected to benefit health. However, the proportion of nonactive commuters who can change their commute mode to active forms remains unclear. The aim of this study was to determine the proportions of nonactive commuters and of those who can change their commute mode to an active form in various regions in Japan. METHODS: In this descriptive study, data were used from an online survey conducted from April to May 2021. Participants included 3,000 adults (20 to 79 years), who were registered with an online survey company. Workers were asked their means of transportation to work and commuting time. Workers using a car or motorcycle for more than 1 minute for commuting were defined as nonactive commuters, and the others were defined as active commuters. Then, nonactive commuters were asked about the possibility of changing their commute mode to active commuting (0%-100%, 11 options in 10% increments). The possibility of change was classified into four groups, i.e., impossible (0%), difficult (10%-40%), probably possible (50%-90%), and possible (100%). The proportions of nonactive commuters and nonactive commuters who can transition to active commuting were described by region. RESULTS: A total of 2,683 participants answered the survey, including 1,647 workers, of whom 1,551 were commuters. The nonactive commuters accounted for 41.4% of commuters overall. The proportion of nonactive commuters was higher in rural than in urban regions. The proportion of nonactive commuters who could change their commute mode was 32.9% of the nonactive commuters or 12.8% of all workers. Among the nonactive commuters, the proportion who could change their commute mode was higher in urban than in rural regions. Of the total workers, the proportion of nonactive commuters who could change their commute mode was higher in rural regions. CONCLUSION: Nonactive commuters accounted for 41.4% of all commuters. The proportion of nonactive commuters who could change their commute mode among nonactive commuters was higher in urban regions. However, in rural regions, as the proportion of nonactive commuters was high, the proportion of nonactive commuters who could change their commute mode among total workers was also high. These results suggest that some of nonactive commuters can change their commute mode from nonactive to active commuting, in rural as well as in urban regions.

The relationship of single-family detached house prices with neighborhood walkability and disaster risk.

People's preferences regarding their neighborhood environment can vary depending on their socioeconomic status and the cities where they live. This study aims to discern the relationship between neighborhood environment factors and single-family detached house sales by sale price and by central and noncentral cities. We analyzed sale prices in the Tokyo Metropolitan Area from 2015 to 2020. The neighborhood environment was assessed using flood/sediment risk and neighborhood walkability measured by net residential density, intersection density, and facility density (walking opportunity). Flood and sediment risk is a major concern that restricts the available land and is included as a negative aspect of the neighborhood environment, taking the topographic features into consideration. A comparison of the results showed that the preference for neighborhood walkability varies by socioeconomic status as well as by target cities. For most facility types, the number of walking opportunities within walking distance from houses was found to be positively related to the sale price of single-family detached houses in all quantiles. The relationship of house price with population and intersection density was found to vary depending on the price level, with a negative relationship with the sale price of relatively more expensive houses being exhibited. People who considered buying houses with relatively higher sale prices were found to devalue houses located in flood/sediment-hazardous areas more. However, it was also found that the negative relationship was slightly mitigated in the highest quantile of sale prices for houses in areas with a moderate flood risk (maximum flooding depth: 3-5 m). Plains near rivers with amenities offer high walkability but pose a flood risk, resulting in a trade-off between flood risk and neighborhood walkability. The findings suggest the use of indices representing diverse preferences in accordance with the target socioeconomic status when policymakers assess the neighborhood environment.

Urban agriculture in walkable neighborhoods bore fruit for health and food system resilience during the COVID-19 pandemic.

Urban agriculture is the key to creating healthy cities and developing resilient urban food systems in uncertain times. However, relevant empirical evidence is limited. This study quantitatively verified the association of access to local food through urban agriculture with subjective well-being, physical activity, and food security concerns of neighborhood communities in the context of the COVID-19 pandemic. The target was Tokyo, Japan, where small-scale local food systems are widespread in walkable neighborhoods. We found that diversity in local food access, ranging from self-cultivation to direct-to-consumer sales, was significantly associated with health and food security variables. In particular, the use of allotment farms was more strongly associated with subjective well-being than the use of urban parks, and it was more strongly associated with the mitigation of food security concerns than the use of food retailers. These findings provide robust evidence for the effectiveness of integrating urban agriculture into walkable neighborhoods.

A simulation of allocation of participants engaging in group activities at community salons: Accessibility and self-stigma.

Community salons are places where older adults receive preventive healthcare and enjoy recreational activities. In Japan, some older adults are reluctant to attend group activity programs at community salons because they do not want to be seen by their neighbors as being elderly who need support from others, even though those activities are meant to prevent functional decline. The phenomenon can be conceptualized as self-stigma of community salon participation, which is a factor explaining why older adults hesitate to participate and some opt for activities at facilities farther away. This paper proposes an allocation problem (considering both accessibility and self-stigma within a Japanese context), demonstrating that participants go to facilities that are farther away, not just those that are closest. The allocation problem is expected to provide local public health agencies with a normative model to assess participants' current allocation (compared with the solutions) and to simulate how best to facilitate older adults' participation or intergroup contact (between those with and without self-stigma). Solutions to the allocation problem are analyzed regarding activity participation, intergroup contact, and distance from participants' home to allocated facilities. Results from the simulation in a virtual city environment show that there could be a segregation of activity groups between people with and without self-stigma. From a comparison among solutions from different geographical settings of residents and facilities, people without self-stigma are less likely to sacrifice their accessibility to allocated facilities in the case of uneven distribution. On the other hand, a larger number of participants with self-stigma is expected, especially in the case of concentrated residential location. The findings suggest that policymakers should consider both the geographical distribution of residents and facilities, the impact of self-stigma, and intergroup contact when they discuss how the policies for older adults' social participation can best result in greater social benefits.

Identifying neurocognitive disorder using vector representation of free conversation.

In recent years, studies on the use of natural language processing (NLP) approaches to identify dementia have been reported. Most of these studies used picture description tasks or other similar tasks to encourage spontaneous speech, but the use of free conversation without requiring a task might be easier to perform in a clinical setting. Moreover, free conversation is unlikely to induce a learning effect. Therefore, the purpose of this study was to develop a machine learning model to discriminate subjects with and without dementia by extracting features from unstructured free conversation data using NLP. We recruited patients who visited a specialized outpatient clinic for dementia and healthy volunteers. Participants' conversation was transcribed and the text data was decomposed from natural sentences into morphemes by performing a morphological analysis using NLP, and then converted into real-valued vectors that were used as features for machine learning. A total of 432 datasets were used, and the resulting machine learning model classified the data for dementia and non-dementia subjects with an accuracy of 0.900, sensitivity of 0.881, and a specificity of 0.916. Using sentence vector information, it was possible to develop a machine-learning algorithm capable of discriminating dementia from non-dementia subjects with a high accuracy based on free conversation.

Efficient oligonucleotide-mediated degradation of nuclear noncoding RNAs in mammalian cultured cells.

Recent large-scale transcriptome analyses have revealed that large numbers of noncoding RNAs (ncRNAs) are transcribed from mammalian genomes. They include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), and longer ncRNAs, many of which are localized to the nucleus, but which have remained functionally elusive. Since ncRNAs are only known to exist in mammalian species, established experimental systems, including the Xenopus oocyte system and yeast genetics, are not available for functional analysis. RNA interference (RNAi), commonly used for analysis of protein-coding genes, is effective in eliminating cytoplasmic mRNAs, but not nuclear RNAs. To circumvent this problem, we have refined the system for knockdown of nuclear ncRNAs with chemically modified chimeric antisense oligonucleotides (ASO) that were efficiently introduced into the nucleus by nucleofection. Under optimized conditions, our system appeared to degrade at least 20 different nuclear ncRNA species in multiple mammalian cell lines with high efficiency and specificity. We also confirmed that our method had greatly improved knockdown efficiency compared with that of the previously reported method in which ASOs are introduced with transfection reagents. Furthermore, we have confirmed the expected phenotypic alterations following knockdown of HBII295 snoRNA and U7 snRNA, which resulted in a loss of site-specific methylation of the artificial RNA and the appearance of abnormal polyadenylated histone mRNA species with a concomitant delay of the cell cycle S phase, respectively. In summary, we believe that our system is a powerful tool to explore the biological functions of the large number of nuclear ncRNAs with unknown function.

Change in walking steps and association with built environments during the COVID-19 state of emergency: A longitudinal comparison with the first half of 2019 in Yokohama, Japan.

In Japan, a state of emergency (SoE) was declared in early April 2020 until late May in response to the first wave of the coronavirus disease (COVID-19). This longitudinal study analyzed the step counts of 18,817 citizens in Yokohama city in the first half of 2020 compared to the previous year, and investigated the association between the change in step counts and the individuals' neighborhood environment by sex and age using generalized linear mixed models. Step counts decreased especially in women and non-elderly people during the SoE. Older women were more susceptible to the neighborhood environment: high walkability (i.e., high population density, proximity to railway stations) adversely affected their step counts, whereas proximity to large parks came to have a positive effect during the SoE.

How Does Urban Farming Benefit Participants' Health? A Case Study of Allotments and Experience Farms in Tokyo.

In Japan, the world's most rapidly aging country, urban farming is attracting attention as an infrastructure for health activities. In Tokyo, urban residents generally participate in two types of farming programs: allotments and experience farms. The availability of regular interaction among participants distinguishes these two programs. We quantitatively examined the difference in changes in self-reported health status between participants in these two types of urban farming. We obtained retrospective cross-sectional data from questionnaire surveys of 783 urban farming participants and 1254 nonparticipants and analyzed the data using ordinal logistic regressions. As a result, compared with nonparticipants, participants in both types of urban farming reported significantly improved self-rated health (SRH) and mental health (MH). After controlling for changes in their physical activity (PA), although participants in allotments did not report significant improvement in SRH and MH, those in experience farms did, suggesting that their health improvement was not only caused by an increase in PA but also by social interaction among participants. From the perspective of health promotion, public support is needed not only for the municipality's allotments but also for the experience farms operated by the farmers themselves.

Inducible expression of microRNA-194 is regulated by HNF-1alpha during intestinal epithelial cell differentiation.

Maintenance of the intestinal epithelium is based on well-balanced molecular mechanisms that confer the stable and continuous supply of specialized epithelial cell lineages from multipotent progenitors. Lineage commitment decisions in the intestinal epithelium system involve multiple regulatory systems that interplay with each other to establish the cellular identities. Here, we demonstrate that the microRNA system could be involved in intestinal epithelial cell differentiation, and that microRNA-194 (miR-194) is highly induced during this process. To investigate this inducible expression mechanism, we identified the genomic structure of the miR-194-2, -192 gene, one of the inducible class of miR-194 parental genes. Furthermore, we identified its transcriptional regulatory region that contains a consensus-binding motif for hepatocyte nuclear factor-1alpha (HNF-1alpha), which is well known as a transcription factor to regulate gene expression in intestinal epithelial cells. By chromatin immunoprecipitation assay and luciferase reporter analysis, we revealed that pri-miR-194-2 expression is controlled by HNF-1alpha, and its consensus binding region is required for the transcription of pri-miR-194-2 in vivo in an intestinal epithelial cell line, Caco-2. Our observations indicate that microRNA genes could be targets of lineage-specific transcription factors and that microRNAs are regulated by a tissue-specific manner in the intestinal epithelium. Therefore, our work suggests that induced expression of these microRNAs have important roles in intestinal epithelium maturation.

Three-Year Longitudinal Association Between Built Environmental Factors and Decline in Older Adults' Step Count: Gaining insights for Age-Friendly Urban Planning and Design.

This study examined the longitudinal association between the change in the step count of older adults and the neighborhood-built environment (BE) in Yokohama, Japan. We analyzed pedometer data in March 2016 and March 2019 that were acquired from 21,557 older adults aged 65-79 years at baseline, who lived in 758 neighborhoods in Yokohama City and participated in the Yokohama Walking Point Program (YWPP). Six BE variables were computed, for each of which neighborhoods were classified into quartiles. Using multilevel regression analysis, we examined the association between the BE variables, baseline step count, and change in step count. Higher population density, lower intersection density, and the second shortest quartile of the average distance to the nearest railway station were associated with a higher baseline step count. A lower intersection density and shorter average distance to the nearest railway station were associated with a smaller decline. The lowest quartile of population density was inversely associated with step-count decline. In conclusion, the neighborhood BEs were not only associated with their step count at baseline, but also widened the disparity of the step count over the three years. These findings would contribute to creating age-friendly cities where older adults can maintain and promote their health.

Modal Shift from Cars and Promotion of Walking by Providing Pedometers in Yokohama City, Japan.

Mobility management is a transportation policy aiming to change travel behavior from car use to sustainable transportation modes while increasing people's physical activity. Providing pedometers and visualizing step counts, popular interventions in public health practice, may constitute a mobility management program. However, the ease of modal shifts and changeability of walking habits differ across neighborhood environments. Using questionnaire data from 2023 middle-aged and older participants from Yokohama, Japan, in May 2017, this study examined (1) the relationship between the physical and social environments of Yokohama Walking Point Program participants who volunteered to use free pedometers and their modal shifts from cars to walking and public transport, and (2) whether participants' modal shifts were associated with increases in step counts. Multivariate categorical regression analyses identified the frequency of greetings and conversations with neighbors as well as health motivation as important explanatory variables in both analyses. Participants living in neighborhoods far from railway stations and in neighborhoods with a high bus stop density tended to shift to walking and public transport, a modal shift that was highly associated with increased step counts. These results suggest that mobility management should be promoted in collaboration with public health and city planning professionals.

Associations between seasonal meteorological conditions and the daily step count of adults in Yokohama, Japan: Results of year-round pedometer measurements in a large population.

People's year-round interpersonal step count variations according to meteorological conditions are not fully understood, because complete year-round data from a sufficient sample of the general population are difficult to acquire. This study examined the associations between meteorological conditions and objectively measured step counts using year-round data collected from a large cohort (N = 24,625) in Yokohama, Japan from April 2015 to March 2016. Two-piece linear regression analysis was used to examine the associations between the monthly median daily step count and three meteorological indices (mean values of temperature, temperature-humidity index (THI), and net effective temperature (NET)). The number of steps per day peaked at temperatures between 19.4 and 20.7 °C. At lower temperatures, the increase in steps per day was between 46.4 and 52.5 steps per 1 °C increase. At temperatures higher than those at which step counts peaked, the decrease in steps per day was between 98.0 and 187.9 per 1 °C increase. Furthermore, these effects were more obvious in elderly than non-elderly persons in both sexes. A similar tendency was seen when using THI and NET instead of temperature. Among the three meteorological indices, the highest R2 value with step counts was observed with THI in all four groups. Both high and low meteorological indices discourage people from walking and higher values of the indices adversely affect step count more than lower values, particularly among the elderly. Among the three indices assessed, THI best explains the seasonal fluctuations in step counts.

Identification of the DNA binding specificity of the human ZNF219 protein and its function as a transcriptional repressor.

The ZNF219 gene is a member of the Kruppel-like zinc finger gene family that is involved in a diverse range of biological processes. The ZNF219 gene encodes a 77-kDa nuclear protein containing nine sets of C2H2 zinc finger structures. By using a random oligonucleotide selection assay and the electromobility gel shift assay, we have revealed that the ZNF219 protein recognizes two copies of CCCCCA. The DNA binding core element is CCCCC. 3' flanking A residues enhance binding of the ZNF219 protein. Use of the various truncated ZNF219 constructs demonstrated that zinc finger 1 to 3 or zinc finger 5 and 6 domains are sufficient to allow specific DNA binding. Both domains independently recognized the same consensus sequence, CCCCCA. Proteins expressed from human cDNA clones KIAA0390 and KIAA0222, which have partial similarities to ZNF219, also showed specific binding to the same core DNA sequence. Potential ZNF219 binding sites were found in the HMGN1 promoter. To examine the function of ZNF219 in the modulation of transcription, we constructed Gal4 DNA binding domain (DBD)/ZNF219 fusion proteins and demonstrated that ZNF219 functioned as a transcriptional repressor for the HMGN1 promoter. Experiments with the truncated ZNF219 constructs suggest that the proline-rich sequence (226-272 a.a., proline content 49%) was responsible for part of the observed repression. These findings provide us with an important start point in our understanding of the functional role of ZNF219 in vivo.