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1.
Asia Pac J Public Health ; 33(4): 404-410, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33715451

RESUMEN

To compare the prevalence of and risk factors associated with overweight or obesity between the international (body mass index [BMI] ≥25 kg/m2) and Asian (BMI ≥23 kg/m2) criteria in a working population in Singapore. This was a cross-sectional analysis of a cohort study of 464 employees (aged ≥21 years) conducted at 4 workplaces in Singapore. The prevalence of overweight or obesity was 47.4% and 67.0% with the international and Asian criteria, respectively. With both the criteria, higher age, male sex, Malay ethnicity (vs Chinese), lower white rice intake, and consumption of sugar-sweetened beverages were positively associated with overweight or obesity. Participants with poorer mental health and higher levels of thermal comfort in the workplace were positively associated with overweight or obesity only with the Asian criteria. The use of international criteria alone in this population could have overlooked these risk factors that are highly relevant to the Singapore context.


Asunto(s)
Índice de Masa Corporal , Técnicas y Procedimientos Diagnósticos , Obesidad , Salud Laboral , Sobrepeso , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Obesidad/diagnóstico , Obesidad/epidemiología , Salud Laboral/estadística & datos numéricos , Sobrepeso/diagnóstico , Sobrepeso/epidemiología , Prevalencia , Reproducibilidad de los Resultados , Factores de Riesgo , Singapur/epidemiología , Lugar de Trabajo , Adulto Joven
3.
Sleep Health ; 6(3): 277-287, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31836498

RESUMEN

OBJECTIVES: We aimed to examine the prevalence of poor sleep quality and short sleep and their associated factors in a working population in Singapore. DESIGN: This is a cross-sectional analysis. SETTING: Four companies in Singapore were included in this study. PARTICIPANTS: Participants included 464 full-time employees (aged ≥21 years). MEASUREMENTS: Self-reported sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Self-administered questionnaires were used to collect data on sociodemographic characteristics, health behaviours, medical history, chronotype, psychosocial factors, health-related quality of life (HRQoL) and occupational factors. Clinical measurements were performed using standard tools and protocols. Multivariate logistic regression was used to examine the factors associated with poor sleep quality (PSQI global score >5) and short sleep (<7 hours/night). RESULTS: The mean age was 39.0 (SD: 11.4) years, and 79.5% were men. The prevalence of poor sleep quality was 42.5%, and 66.2% were short sleepers. Nearly three-fourths (71.3%) had at least one of these two conditions. Age, Malay ethnicity (vs. Chinese), chronic conditions, poorer mental health, stress at home or work and shift work were positively associated, and mental component summary of the HRQoL scale and work years in the current company were negatively associated with poor sleep quality. Age, Malay and Indian ethnicities (vs. Chinese), longer dinner-to-bed time, snacking between dinner and bed time, and poorer mental health were positively associated with short sleep. CONCLUSIONS: Poor sleep quality and short sleep were highly common in this working population in Singapore. Workplace policies should include education and intervention programmes to promote better sleep hygiene.


Asunto(s)
Privación de Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Adulto , Estudios Transversales , Empleo/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Laboral , Prevalencia , Factores de Riesgo , Autoinforme , Singapur/epidemiología , Lugar de Trabajo
4.
Artículo en Inglés | MEDLINE | ID: mdl-31881679

RESUMEN

Little is known about the effect of working conditions on vitamin D status in Southeast Asia, where vitamin D deficiency is common despite the presence of sunlight all year round in most places. We examined the prevalence of vitamin D deficiency and its associated work-related factors among indoor workers using the data of 213 participants (aged ≥21 years) from a workplace cohort study in Singapore. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/L. Data on work-related factors, socio-demographic characteristics, and lifestyle habits were collected using standardized questionnaires. Clinical and biochemical measurements were performed using standard tools and protocols. Multivariate Poisson regression was used to examine the independent association of work-related factors with vitamin D deficiency. Mean serum 25(OH)D concentration was 59.6 nmol/L. The prevalence of vitamin D deficiency was 32.9% (95% confidence interval (CI): 26.6-39.6%). In the multivariate analysis, office workers (prevalence ratio (PR): 2.16, 95% CI: 1.12-4.16 versus control room workers), workshop workers (PR: 2.25, 95% CI: 1.05-4.81 versus control room workers), and night shift workers (PR: 1.31, 95% CI: 1.03-1.67) were at a greater risk for vitamin D deficiency. Workplace policies and wellness programs should encourage workers to take regular breaks to go outdoors for sunlight exposure and to consume adequate amounts of vitamin D-rich foods to maintain optimal vitamin D levels.


Asunto(s)
Luz Solar , Deficiencia de Vitamina D/sangre , Vitamina D/análogos & derivados , Lugar de Trabajo , Adulto , Calcifediol/administración & dosificación , Estudios de Cohortes , Estudios Transversales , Etnicidad , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Prevalencia , Singapur , Encuestas y Cuestionarios , Vitamina D/sangre , Vitaminas/administración & dosificación , Adulto Joven
5.
Artículo en Inglés | MEDLINE | ID: mdl-31752089

RESUMEN

We aimed to examine the behavioural and clinical risk factors for non-communicable diseases (NCDs) at baseline and their changes over 12 months in a workplace cohort in Singapore. A total of 464 full-time employees (age ≥ 21 years) were recruited from a variety of occupational settings, including offices, control rooms, and workshops. Of these, 424 (91.4%) were followed-up at three months and 334 (72.0%) were followed up at 12 months. Standardized questionnaires were used to collect data on health behaviours and clinical measurements were performed by trained staff using standard instruments and protocols. Age-adjusted changes in risk factors over time were examined using generalized estimating equations or linear mixed-effects models where appropriate. The mean age of the participants at baseline was 39.0 (SD: 11.4) years and 79.5% were men. Nearly a quarter (24.4%) were current smokers, slightly more than half (53.5%) were alcohol drinkers, two-thirds (66%) were consuming <5 servings of fruit and vegetables per day, and 23.1% were physically inactive. More than two-thirds (67%) were overweight or obese and 34.5% had central obesity. The mean follow-up was 8.6 months. After adjusting for age, over 12 months, there was a significant increase in the proportion consuming <5 servings of fruit and vegetables per day by 33% (p = 0.030), who were physically inactive by 64% (p < 0.001), and of overweight or obese people by 15% (p = 0.018). The burden of several key NCD risk factors at baseline was high and some worsened within a short period of time in this working population. There is a need for more targeted strategies for behaviour change towards a healthy lifestyle as part of the ongoing health and wellness programs at workplaces in Singapore.


Asunto(s)
Enfermedades no Transmisibles/epidemiología , Enfermedades Profesionales/epidemiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/etiología , Prevalencia , Factores de Riesgo , Singapur/epidemiología , Lugar de Trabajo/estadística & datos numéricos , Adulto Joven
6.
J Med Internet Res ; 21(5): e13868, 2019 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-31124462

RESUMEN

BACKGROUND: The World Health Organization states that 35% of women experience domestic violence at least once during their lifetimes. However, approximately 80% of health professionals have never received any training on management of this major public health concern. OBJECTIVE: The objective of this study was to evaluate the effectiveness of health professions digital education on domestic violence compared to that of traditional ways or no intervention. METHODS: Seven electronic databases were searched for randomized controlled trials from January 1990 to August 2017. The Cochrane Handbook guideline was followed, and studies reporting the use of digital education interventions to educate health professionals on domestic violence management were included. RESULTS: Six studies with 631 participants met our inclusion criteria. Meta-analysis of 5 studies showed that as compared to control conditions, digital education may improve knowledge (510 participants and 5 studies; standardized mean difference [SMD] 0.67, 95% CI 0.38-0.95; I2=59%; low certainty evidence), attitudes (339 participants and 3 studies; SMD 0.67, 95% CI 0.25-1.09; I2=68%; low certainty evidence), and self-efficacy (174 participants and 3 studies; SMD 0.47, 95% CI 0.16-0.77; I2=0%; moderate certainty evidence). CONCLUSIONS: Evidence of the effectiveness of digital education on health professionals' understanding of domestic violence is promising. However, the certainty of the evidence is predominantly low and merits further research. Given the opportunity of scaled transformative digital education, both further research and implementation within an evaluative context should be prioritized.


Asunto(s)
Violencia Doméstica/psicología , Educación en Salud/métodos , Personal de Salud/educación , Femenino , Humanos , Masculino
7.
J Med Internet Res ; 21(4): e12968, 2019 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-31017584

RESUMEN

BACKGROUND: The shortage and disproportionate distribution of health care workers worldwide is further aggravated by the inadequacy of training programs, difficulties in implementing conventional curricula, deficiencies in learning infrastructure, or a lack of essential equipment. Offline digital education has the potential to improve the quality of health professions education. OBJECTIVE: The primary objective of this systematic review was to evaluate the effectiveness of offline digital education compared with various controls in improving learners' knowledge, skills, attitudes, satisfaction, and patient-related outcomes. The secondary objectives were (1) to assess the cost-effectiveness of the interventions and (2) to assess adverse effects of the interventions on patients and learners. METHODS: We searched 7 electronic databases and 2 trial registries for randomized controlled trials published between January 1990 and August 2017. We used Cochrane systematic review methods. RESULTS: A total of 27 trials involving 4618 individuals were included in this systematic review. Meta-analyses found that compared with no intervention, offline digital education (CD-ROM) may increase knowledge in nurses (standardized mean difference [SMD]=1.88; 95% CI 1.14 to 2.62; participants=300; studies=3; I2=80%; low certainty evidence). A meta-analysis of 2 studies found that compared with no intervention, the effects of offline digital education (computer-assisted training [CAT]) on nurses and physical therapists' knowledge were uncertain (SMD 0.55; 95% CI -0.39 to 1.50; participants=64; I2=71%; very low certainty evidence). A meta-analysis of 2 studies found that compared with traditional learning, a PowerPoint presentation may improve the knowledge of patient care personnel and pharmacists (SMD 0.76; 95% CI 0.29 to 1.23; participants=167; I2=54%; low certainty evidence). A meta-analysis of 4 studies found that compared with traditional training, the effects of computer-assisted training on skills in community (mental health) therapists, nurses, and pharmacists were uncertain (SMD 0.45; 95% CI -0.35 to 1.25; participants=229; I2=88%; very low certainty evidence). A meta-analysis of 4 studies found that compared with traditional training, offline digital education may have little effect or no difference on satisfaction scores in nurses and mental health therapists (SMD -0.07; 95% CI -0.42 to 0.28, participants=232; I2=41%; low certainty evidence). A total of 2 studies found that offline digital education may have little or no effect on patient-centered outcomes when compared with blended learning. For skills and attitudes, the results were mixed and inconclusive. None of the studies reported adverse or unintended effects of the interventions. Only 1 study reported costs of interventions. The risk of bias was predominantly unclear and the certainty of the evidence ranged from low to very low. CONCLUSIONS: There is some evidence to support the effectiveness of offline digital education in improving learners' knowledge and insufficient quality and quantity evidence for the other outcomes. Future high-quality studies are needed to increase generalizability and inform use of this modality of education.


Asunto(s)
Educación en Salud/métodos , Empleos en Salud/normas , Personal de Salud/educación , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
J Med Internet Res ; 21(3): e13165, 2019 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-30907731

RESUMEN

BACKGROUND: Medical schools in low- and middle-income countries are facing a shortage of staff, limited infrastructure, and restricted access to fast and reliable internet. Offline digital education may be an alternative solution for these issues, allowing medical students to learn at their own time and pace, without the need for a network connection. OBJECTIVE: The primary objective of this systematic review was to assess the effectiveness of offline digital education compared with traditional learning or a different form of offline digital education such as CD-ROM or PowerPoint presentations in improving knowledge, skills, attitudes, and satisfaction of medical students. The secondary objective was to assess the cost-effectiveness of offline digital education, changes in its accessibility or availability, and its unintended/adverse effects on students. METHODS: We carried out a systematic review of the literature by following the Cochrane methodology. We searched seven major electronic databases from January 1990 to August 2017 for randomized controlled trials (RCTs) or cluster RCTs. Two authors independently screened studies, extracted data, and assessed the risk of bias. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We included 36 studies with 3325 medical students, of which 33 were RCTs and three were cluster RCTs. The interventions consisted of software programs, CD-ROMs, PowerPoint presentations, computer-based videos, and other computer-based interventions. The pooled estimate of 19 studies (1717 participants) showed no significant difference between offline digital education and traditional learning groups in terms of students' postintervention knowledge scores (standardized mean difference=0.11, 95% CI -0.11 to 0.32; small effect size; low-quality evidence). Meta-analysis of four studies found that, compared with traditional learning, offline digital education improved medical students' postintervention skills (standardized mean difference=1.05, 95% CI 0.15-1.95; large effect size; low-quality evidence). We are uncertain about the effects of offline digital education on students' attitudes and satisfaction due to missing or incomplete outcome data. Only four studies estimated the costs of offline digital education, and none reported changes in accessibility or availability of such education or in the adverse effects. The risk of bias was predominantly high in more than half of the included studies. The overall quality of the evidence was low (for knowledge, skills, attitudes, and satisfaction) due to the study limitations and inconsistency across the studies. CONCLUSIONS: Our findings suggest that offline digital education is as effective as traditional learning in terms of medical students' knowledge and may be more effective than traditional learning in terms of medical students' skills. However, there is a need to further investigate students' attitudes and satisfaction with offline digital education as well as its cost-effectiveness, changes in its accessibility or availability, and any resulting unintended/adverse effects.


Asunto(s)
Educación Médica/métodos , Educación en Salud/métodos , Estudiantes de Medicina/psicología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
J Med Internet Res ; 21(1): e12959, 2019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30668519

RESUMEN

BACKGROUND: Virtual reality (VR) is a technology that allows the user to explore and manipulate computer-generated real or artificial three-dimensional multimedia sensory environments in real time to gain practical knowledge that can be used in clinical practice. OBJECTIVE: The aim of this systematic review was to evaluate the effectiveness of VR for educating health professionals and improving their knowledge, cognitive skills, attitudes, and satisfaction. METHODS: We performed a systematic review of the effectiveness of VR in pre- and postregistration health professions education following the gold standard Cochrane methodology. We searched 7 databases from the year 1990 to August 2017. No language restrictions were applied. We included randomized controlled trials and cluster-randomized trials. We independently selected studies, extracted data, and assessed risk of bias, and then, we compared the information in pairs. We contacted authors of the studies for additional information if necessary. All pooled analyses were based on random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the body of evidence. RESULTS: A total of 31 studies (2407 participants) were included. Meta-analysis of 8 studies found that VR slightly improves postintervention knowledge scores when compared with traditional learning (standardized mean difference [SMD]=0.44; 95% CI 0.18-0.69; I2=49%; 603 participants; moderate certainty evidence) or other types of digital education such as online or offline digital education (SMD=0.43; 95% CI 0.07-0.79; I2=78%; 608 participants [8 studies]; low certainty evidence). Another meta-analysis of 4 studies found that VR improves health professionals' cognitive skills when compared with traditional learning (SMD=1.12; 95% CI 0.81-1.43; I2=0%; 235 participants; large effect size; moderate certainty evidence). Two studies compared the effect of VR with other forms of digital education on skills, favoring the VR group (SMD=0.5; 95% CI 0.32-0.69; I2=0%; 467 participants; moderate effect size; low certainty evidence). The findings for attitudes and satisfaction were mixed and inconclusive. None of the studies reported any patient-related outcomes, behavior change, as well as unintended or adverse effects of VR. Overall, the certainty of evidence according to the GRADE criteria ranged from low to moderate. We downgraded our certainty of evidence primarily because of the risk of bias and/or inconsistency. CONCLUSIONS: We found evidence suggesting that VR improves postintervention knowledge and skills outcomes of health professionals when compared with traditional education or other types of digital education such as online or offline digital education. The findings on other outcomes are limited. Future research should evaluate the effectiveness of immersive and interactive forms of VR and evaluate other outcomes such as attitude, satisfaction, cost-effectiveness, and clinical practice or behavior change.


Asunto(s)
Educación en Salud/métodos , Empleos en Salud/normas , Personal de Salud/educación , Realidad Virtual , Humanos
10.
Wound Repair Regen ; 27(1): 114-125, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30362646

RESUMEN

Chronic wounds are a health problem that have devastating consequences for patients and contribute major costs to healthcare systems and societies. To understand the magnitude of this health issue, a systematic review was undertaken. Searches were conducted in MEDLINE, EMBASE, EBM Reviews and Cochrane library, CINAHL, EBSCO, PsycINFO, and Global Health databases for articles published between 2000 and 2015. Included publications had to target adults (≥18 years of age), state wound chronicity (≥3 weeks) and/or label the wounds as chronic, complex, hard-to-heal, or having led to an amputation. The review excluded studies that did not present data on generic health-related quality of life and/or cost data, case studies, randomized controlled trials, economic modeling studies, abstracts, and editorials. Extracted data were summarized into a narrative synthesis, and for a few articles using the same health-related quality of life instrument, average estimates with 95% confidence intervals were calculated. Thirty articles met the inclusion criteria. Findings revealed that health-related quality of life was lowest for physical pathologies, and based on average estimates were scores most inferior in the domain physical role for both patients with chronic wounds and for those with wound-related amputations. The cost burden was mainly attributed to amputations for patients also comorbid with diabetes, where the cost for hospitalization ranged from US$12,851 to US$16,267 (median) for this patient group. Patients with chronic wounds have poor health-related quality of life in general and wound-related costs are substantial. Development and implementation of wound management strategies that focus on increasing health-related quality of life and effectively reduce costs for this patient group are urgently needed.


Asunto(s)
Enfermedad Crónica/economía , Costo de Enfermedad , Costos de la Atención en Salud/estadística & datos numéricos , Cicatrización de Heridas/fisiología , Heridas y Lesiones/economía , Enfermedad Crónica/psicología , Enfermedad Crónica/terapia , Humanos , Calidad de Vida/psicología , Heridas y Lesiones/psicología , Heridas y Lesiones/terapia
11.
BMC Med ; 16(1): 18, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-29397794

RESUMEN

BACKGROUND: Our aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved. METHODS: An umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken. The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised. The following databases were searched: MEDLINE, EMBASE, Web of Science, CENTRAL, PsycINFO and CINAHL. In addition, reference lists were screened. We included reviews of the effects of MLT on any type of health-related outcome measure. RESULTS: Altogether, 195 reviews met the inclusion criteria. Most were of low methodological quality (mean -4.5, standard deviation 6.7). Of those, 164 did not pool the data and were synthesised narratively (qualitatively) whereas the remaining 31 used meta-analytic techniques and were synthesised quantitatively. Seven meta-analyses were significant with P values less than 0.001 under the random-effects model. These pertained to sleep latency, pre-operative anxiety, prevention of agitation and risk of breast cancer. CONCLUSIONS: There is an abundance of reviews evaluating the effects of exogenous and endogenous MLT on health. In general, MLT has been shown to be associated with a wide variety of health outcomes in clinically and methodologically heterogeneous populations. Many reviews stressed the need for more high-quality randomised clinical trials to reduce the existing uncertainties.


Asunto(s)
Ansiedad/tratamiento farmacológico , Ritmo Circadiano/fisiología , Melatonina/uso terapéutico , Calidad de Vida/psicología , Humanos
12.
Stem Cells ; 34(4): 860-72, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26864965

RESUMEN

During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE-1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we found that REST knockout cells lost the ability to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective downregulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals. REST regulates cardiac differentiation of ESCs by negatively regulating the Wnt/ß-catenin signaling pathway and positively regulating the cardiogenic TF Gata4. We propose here a new role for REST in cell fate specification besides its well-known repressive role of neuronal differentiation.


Asunto(s)
Diferenciación Celular/genética , Factor de Transcripción GATA4/biosíntesis , Células Madre Embrionarias de Ratones/metabolismo , Proteínas Represoras/genética , Animales , Linaje de la Célula/genética , Factor de Transcripción GATA4/genética , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Vía de Señalización Wnt
13.
Stem Cells ; 31(12): 2632-46, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23963638

RESUMEN

The unique ability of Sox2 to cooperate with Oct4 at selective binding sites in the genome is critical for reprogramming somatic cells into induced pluripotent stem cells (iPSCs). We have recently demonstrated that Sox17 can be converted into a reprogramming factor by alteration of a single amino acid (Sox17EK) within its DNA binding HMG domain. Here we expanded this study by introducing analogous mutations to 10 other Sox proteins and interrogated the role of N-and C-termini on the reprogramming efficiency. We found that point-mutated Sox7 and Sox17 can convert human and mouse fibroblasts into iPSCs, but Sox4, Sox5, Sox6, Sox8, Sox9, Sox11, Sox12, Sox13, and Sox18 cannot. Next we studied regions outside the HMG domain and found that the C-terminal transactivation domain of Sox17 and Sox7 enhances the potency of Sox2 in iPSC assays and confers weak reprogramming potential to the otherwise inactive Sox4EK and Sox18EK proteins. These results suggest that the glutamate (E) to lysine (K) mutation in the HMG domain is necessary but insufficient to swap the function of Sox factors. Moreover, the HMG domain alone fused to the VP16 transactivation domain is able to induce reprogramming, albeit at low efficiency. By molecular dissection of the C-terminus of Sox17, we found that the ß-catenin interaction region contributes to the enhanced reprogramming efficiency of Sox17EK. To mechanistically understand the enhanced reprogramming potential of Sox17EK, we analyzed ChIP-sequencing and expression data and identified a subset of candidate genes specifically regulated by Sox17EK and not by Sox2.


Asunto(s)
Células Madre Pluripotentes Inducidas/fisiología , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Factores de Transcripción SOXF/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Técnicas de Cultivo de Célula , Reprogramación Celular/genética , Reprogramación Celular/fisiología , Proteínas HMGB/genética , Proteínas HMGB/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/trasplante , Ratones , Ratones SCID , Factor 3 de Transcripción de Unión a Octámeros/genética , Mutación Puntual , Factores de Transcripción SOXF/genética , Activación Transcripcional , beta Catenina/metabolismo
14.
EMBO J ; 32(7): 938-53, 2013 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-23474895

RESUMEN

How regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We show that Sox17 partners with Oct4 and binds to a unique 'compressed' Sox/Oct motif that earmarks endodermal genes. This is in contrast to the pluripotent state where Oct4 selectively partners with Sox2 at 'canonical' binding sites. The distinct selection of binding sites by alternative Sox/Oct partnering is underscored by our demonstration that rationally point-mutated Sox17 partners with Oct4 on pluripotency genes earmarked by the canonical Sox/Oct motif. In an endodermal differentiation assay, we demonstrate that the compressed motif is required for proper expression of endodermal genes. Evidently, Oct4 drives alternative developmental programs by switching Sox partners that affects enhancer selection, leading to either an endodermal or pluripotent cell fate. This work provides insights in understanding cell fate transcriptional regulation by highlighting the direct link between the DNA sequence of an enhancer and a developmental outcome.


Asunto(s)
Embrión de Mamíferos/embriología , Endodermo/embriología , Elementos de Facilitación Genéticos/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas HMGB/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXF/metabolismo , Secuencias de Aminoácidos , Animales , Sitios de Unión , Diferenciación Celular/fisiología , Línea Celular , Embrión de Mamíferos/citología , Endodermo/citología , Proteínas HMGB/genética , Ratones , Factor 3 de Transcripción de Unión a Octámeros/genética , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXF/genética , Transcripción Genética/fisiología
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