Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis.

Cuproptosis, a new type of copper-induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib-resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM-regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.

Disturbing NLRP3 acetylation and inflammasome assembly inhibits androgen receptor-promoted inflammatory responses and prostate cancer progression.

Chronic inflammation is one of the definite factors leading to the occurrence and development of tumors, including prostate cancer (PCa). The androgen receptor (AR) pathway is essential for PCa tumorigenesis and inflammatory response. However, little is known about the AR-regulated NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome pathway in human PCa. In this study, we explored the expression of inflammatory cytokine and AR in high-grade PCa and observed that NLRP3 inflammasome-associated genes were upregulated in high-grade PCa compared with that in low-grade PCa and benign prostatic hyperplasia and were associated with AR expression. In addition, we identified circAR-3-a circRNA derived from the AR gene-which is involved in the AR-regulated inflammatory response and cell proliferation by activating the NLRP3 inflammatory pathway. While circAR-3 overexpression promoted cell proliferation and the inflammatory response, its depletion induced opposite effects. Mechanistically, we noted that circAR-3 mediated the acetylation modification of NLRP3 by KAT2B and then promoted NLRP3 inflammasome complex subcellular distribution and assembly. Disturbing NLRP3 acetylation or blocking inflammasome assembly with an inhibitor suppressed the progression of PCa xenograft tumors. Our findings provide the first evidence that targeting NLRP3 acetylation or inflammasome assembly may be effective in inhibiting PCa progression.

HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis.

The activity of hematopoietic factor GATA-1 is modulated through p300/CBP-mediated acetylation and FOG-1 mediated indirect interaction with HDAC1/2 containing NuRD complex. Although GATA-1 acetylation is implicated in GATA-1 activation, the role of deacetylation is not studied. Here, we found that the FOG-1/NuRD does not deacetylate GATA-1. However, HDAC1/2 can directly bind and deacetylate GATA-1. Two arginine residues within the GATA-1 linker region mediates direct interaction with HDAC1. The arginine to alanine mutation (2RA) blocks GATA-1 deacetylation and fails to induce erythroid differentiation. Gene expression profiling and ChIP-seq analysis further demonstrate the importance of GATA-1 deacetylation for gene activation and chromatin recruitment. GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.

Evaluating the In Vitro and In Vivo Prebiotic Effects of Different Xylo-Oligosaccharides Obtained from Bamboo Shoots by Hydrothermal Pretreatment Combined with Endo-Xylanase Hydrolysis.

Xylo-oligosaccharides (XOS) enriched with high fractions of X2-X3 are regarded as an effective prebiotic for regulating the intestinal microflora. In this study, the original XOS solution was obtained from bamboo shoots through hydrothermal pretreatment under optimized conditions. Subsequently, enzymatic hydrolysis with endo-xylanase was performed on the original XOS solution to enhance the abundance of the X2-X3 fractions. The results demonstrated that hydrothermal pretreatment yielded 21.24% of XOS in the hydrolysate solution, and subsequent enzymatic hydrolysis significantly increased the proportion of the X2-X3 fractions from 38.87% to 68.21%. Moreover, the XOS solutions with higher amounts of X2-X3 fractions exhibited superior performance in promoting the growth of probiotics such as Bifidobacterium adolescentis and Lactobacillus acidophilus in vitro, leading to increased production of short-chain fatty acids. In the in vivo colitis mouse model, XOS solutions with higher contents of X2-X3 fractions demonstrated enhanced efficacy against intestinal inflammation. Compared with the colitis mice (model group), the XOS solution with higher X2-X3 fractions (S1 group) could significantly increase the number of Streptomyces in the intestinal microflora, while the original XOS solution (S2 group) could significantly increase the number of Bacteroides in the intestinal microflora of colitis mice. In addition, the abundances of Alcaligenes and Pasteurella in the intestinal microflora of the S1 and S2 groups were much lower than in the model group. This effect was attributed to the ability of these XOS solutions to enhance species diversity, reversing the imbalance and disorder within the intestinal microflora. Overall, this work highlights the outstanding potential of XOS enriched with high contents of X2-X3 fractions as a regulator of the intestinal microbiota and as an anti-colitis agent.

Bioluminescence imaging of mouse monocyte chemoattractant protein-1 expression in inflammatory processes.

Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in various inflammatory diseases. To reveal the impact of MCP-1 during diseases and to develop anti-inflammatory agents, we establish a transgenic mouse line. The firefly luciferase gene is incorporated into the mouse genome and driven by the endogenous MCP-1 promoter. A bioluminescence photographing system is applied to monitor luciferase levels in live mice during inflammation, including lipopolysaccharide-induced sepsis, concanavalin A-induced T cell-dependent liver injury, CCl 4-induced acute hepatitis, and liver fibrosis. The results demonstrate that the luciferase signal induced in inflammatory processes is correlated with endogenous MCP-1 expression in mice. Furthermore, the expressions of MCP-1 and the luciferase gene are dramatically inhibited by administration of the anti-inflammatory drug dexamethasone in a septicemia model. Our results suggest that the transgenic MCP-1-Luc mouse is a useful model to study MCP-1 expression in inflammation and disease and to evaluate the efficiency of anti-inflammatory drugs in vivo.

A Single Amino Acid Substitution in MIL1 Leads to Activation of Programmed Cell Death and Defense Responses in Rice.

Lesion mimic mutants are an ideal model system for elucidating the molecular mechanisms of programmed cell death and defense responses in rice. In this study, we identified a lesion mimic mutant termed miner infection like 1-1 (mil1-1). The mil1-1 exhibited lesions on the leaves during development, and the chloroplasts of mil1-1 leaves were disrupted. Reactive oxygen species were found to accumulate in mil1-1 leaves. Cell death and DNA fragmentation were observed in mil1-1 leaves, indicating that the cells in the spots of mil1-1 leaves experienced programmed cell death. Most agronomic traits decreased in mil1-1, suggesting that the growth retardation in mil1-1 caused reduced per-plant grain yield. However, the mutation of MIL1 activated the expression of pathogen response genes and enhanced resistance to bacterial blight. The MIL1 gene was cloned using the positional cloning approach. A missense mutation 751 bp downstream of ATG was found in mil1-1. The defects of mil1-1 were able to be rescued by delivering a wild-type MIL1 gene into mil1-1. MIL1 encoded hydroperoxide lyase 3 (OsHPL3), and the expression of OsHPL3 was induced via hormone and abiotic stresses. Our findings provide insights into the roles of MIL1 in regulating programmed cell death, development, yield, and defense responses in rice.

Liutex-Represented Vortex Spectrum in Turbulence.

The Liutex vector is new quantity introduced to represent the rigid-body rotation part of fluid motion and thus to define and identify vortices in various flows. In this work, the intermittency and power-law similarity of the Liutex vector in homogeneous, isotropic turbulence and a turbulent channel are explored. First, we found that the Liutex vector is more intermittent than the vorticity vector in the considered turbulent flows, which indicates that an iso-surface of a Liutex magnitude with an appropriate threshold could capture the major rotating motions or vortical motions of the flow. Second, the three-dimensional energy spectrums of velocity, vorticity (enstrophy spectrum) and the Liutex vector in homogeneous isotropic turbulence are shown to exhibit power laws of -5/3, 1/3 and 1/3 in the inertial subrange, respectively, whilst the Liutex energy spectrum particularly satisfies an additional -10/3 power law in the viscous subrange. This viscous similarity of the Liutex vector is the only power law that survived from the wall presence and is argued to originate from the fact that the Liutex vector represents the rigid part of fluid motion and is free from any shear contamination. The existence of such a viscous similarity law indicates a certain coherence of the small scales of turbulence and could possibly help understand and model turbulence.

LAZY1 Controls Tiller Angle and Shoot Gravitropism by Regulating the Expression of Auxin Transporters and Signaling Factors in Rice.

Tiller angle is a key factor determining rice plant architecture, planting density, light interception, photosynthetic efficiency, disease resistance and grain yield. However, the mechanisms underlying tiller angle control are far from clear. In this study, we identified a mutant, termed bta1-1, with an enlarged tiller angle throughout its life cycle. A detailed analysis reveals that BTA1 has multiple functions because tiller angle, shoot gravitropism and tolerance to drought stress are changed in bta1-1 plants. Moreover, BTA1 is a positive regulator of shoot gravitropism in rice. Shoot responses to gravistimulation are disrupted in bta1-1 under both light and dark conditions. Gene cloning reveals that bta1-1 is a novel mutant allele of LA1 renamed la1-SN. LA1 is able to rescue the tiller angle and shoot gravitropism defects observed in la1-SN. The nuclear localization signal of LA1 is disrupted by la1-SN, causing changes in its subcellular localization. LA1 is required to regulate the expression of auxin transporters and signaling factors that control shoot gravitropism and tiller angle. High-throughput mRNA sequencing is performed to elucidate the molecular and cellular functions of LA1. The results show that LA1 may be involved in the nucleosome and chromatin assembly, and protein-DNA interactions to control gene expression, shoot gravitropism and tiller angle. Our results provide new insight into the mechanisms whereby LA1 controls shoot gravitropism and tiller angle in rice.

Genome-wide identification and phylogenetic analysis of rice FTIP gene family.

FT-INTERACTING PROTEIN (FTIP) gene family in rice are the members of multiple C2 domain and transmembrane region proteins (MCTPs). There are many homologs of OsFTIPs in plants; however, the bioinformatics of them remains unclear. In the studies, 13 OsFTIP genes are identified in rice. OsFTIPs are unevenly located in 12 chromosomes. The OsFTIPs are phylogenetically divided into three clades. Cis-elements respond to abiotic stress, light, and hormones are found in the promoter region of OsFTIPs which are induced by the stimuli. All OsFTIPs are expressed with different profiles. Syntenic analysis of 128 OsFTIPs and FTIP-like homologs reveals that various number of gene pairs are identified between rice and other species. The 128 FTIP-like homologs are divided into six groups which fall into three classes. Ten motifs are shared by most OsFTIPs and their homologs. The studies provide a theoretical basis for further elucidating the functions of OsFTIP gene family.

Effect of lipase incorporation on gelling properties of catfish (Clarias lazera) surimi and its mechanism.

BACKGROUND: Recently, fatty fish have been utilized as a potential approach for the fabrication of surimi products, with the yield of fatty fish surimi being > 10 000 tons in 2019. However, the gelling properties of catfish surimi can be influenced by intermuscular lipid. Lipase could effectively enhance the gel quality of catfish surimi gels, although the chemical forces involved in gel formation and alteration in lipid and protein oxidation status are not well understood. The present study investigated the gelation-enhancing effects of lipase on catfish surimi based on changes in chemical oxidation interactions. RESULTS: The addition of 7.5 g kg-1 lipase significantly increased the hydrophobic interactions and disulfide bond contents, both of which facilitated gel formation, in surimi gels. The 2-thiobarbituric acid reactive substance and carbonyl concentrations demonstrated that lipase promoted lipid and protein oxidations. Furthermore, an appropriate dose of malondialdehyde accelerated protein oxidation, thereby resulting in the covalent cross-linking of proteins. Consequently, the gel strength increased from 55.72 to 127.71 g × cm with lipase contents of up to 7.5 g kg-1 , and strong chemical cross-linking and a compact network were observed via sodium dodecyl sulfate polyacrylamide gel electrophoresis and scanning electron microscopy. However, excessive oxidation led to the degeneration of the gel matrix. A schematic mechanism, mainly based on the chemical changes, is proposed. CONCLUSION: The present study revealed the gelation mechanism of catfish surimi gels with lipase, and suggested that lipase treatments may be an effective approach for improving the textural properties of fatty fish surimi gels. © 2021 Society of Chemical Industry.

CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia.

HOX gene dysregulation is a common feature of acute myeloid leukemia (AML). The molecular mechanisms underlying aberrant HOX gene expression and associated AML pathogenesis remain unclear. The nuclear protein CCCTC-binding factor (CTCF), when bound to insulator sequences, constrains temporal HOX gene-expression patterns within confined chromatin domains for normal development. Here, we used targeted pooled CRISPR-Cas9-knockout library screening to interrogate the function of CTCF boundaries in the HOX gene loci. We discovered that the CTCF binding site located between HOXA7 and HOXA9 genes (CBS7/9) is critical for establishing and maintaining aberrant HOXA9-HOXA13 gene expression in AML. Disruption of the CBS7/9 boundary resulted in spreading of repressive H3K27me3 into the posterior active HOXA chromatin domain that subsequently impaired enhancer/promoter chromatin accessibility and disrupted ectopic long-range interactions among the posterior HOXA genes. Consistent with the role of the CBS7/9 boundary in HOXA locus chromatin organization, attenuation of the CBS7/9 boundary function reduced posterior HOXA gene expression and altered myeloid-specific transcriptome profiles important for pathogenesis of myeloid malignancies. Furthermore, heterozygous deletion of the CBS7/9 chromatin boundary in the HOXA locus reduced human leukemic blast burden and enhanced survival of transplanted AML cell xenograft and patient-derived xenograft mouse models. Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies.

Knowing When to Silence: Roles of Polycomb-Group Proteins in SAM Maintenance, Root Development, and Developmental Phase Transition.

Polycomb repressive complex 1 (PRC1) and PRC2 are the major complexes composed of polycomb-group (PcG) proteins in plants. PRC2 catalyzes trimethylation of lysine 27 on histone 3 to silence target genes. Like Heterochromatin Protein 1/Terminal Flower 2 (LHP1/TFL2) recognizes and binds to H3K27me3 generated by PRC2 activities and enrolls PRC1 complex to further silence the chromatin through depositing monoubiquitylation of lysine 119 on H2A. Mutations in PcG genes display diverse developmental defects during shoot apical meristem (SAM) maintenance and differentiation, seed development and germination, floral transition, and so on so forth. PcG proteins play essential roles in regulating plant development through repressing gene expression. In this review, we are focusing on recent discovery about the regulatory roles of PcG proteins in SAM maintenance, root development, embryo development to seedling phase transition, and vegetative to reproductive phase transition.

Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis.

Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.

Quality Enhancement Mechanism of Alkali-Free Chinese Northern Steamed Bread by Sourdough Acidification.

Alkali was used to adjust the pH and neutralize the excess acids of dough in the processing of Chinese northern steamed bread (CNSB). However, extra alkali addition generally resulted in alkalic flavor and poor appearance. The aim of this work was to investigate the role of proofed dough pH on the texture of CNSB. Correlation analysis demonstrated that the pH value of proofed dough has a significant effect on the textural properties of CNSB. The mechanism studies found that gradual acidification of dough by lactic acid bacteria is a critical factor affecting the process. Conversely, chemical acidification weakened the texture property of products and reduced the dough rheology. Scanning electron microscope (SEM) analysis showed that fermentation with starter for 12 h produced a continuous and extensional protein network in the proofed dough. Furthermore, the decreasing pH of proofed dough increased the extractability of protein in a sodium dodecyl sulfate (SDS)-containing medium and the content of free sulfhydryl (SH). The structure and content of gluten, especially influenced by gradual acidification level, change the quality of the final product. It is a novel approach to obtain an alkali-free CNSB with excellent quality by moderate gluten adjustment.

Adsorption of fluoride from aqueous solution by fly ash cenospheres modified with paper mill lime mud: Experimental and modeling.

Fluoride removal from aqueous solution by adsorption using fly ash cenospheres (FAC) modified with paper mill lime mud (LM) as composite adsorbent had been investigated. The characterization of FAC and composite adsorbent were analyzed by Scanning electron spectroscope (SEM), Energy dispersive spectrometer (EDS), Brunauer emmett teller (BET) and Fourier transform infrared (FTIR), which demonstrated that the porous structure of composite adsorbent was obtained after surface modification. Adsorption of fluoride on modified fly ash cenospheres was fitted with pseudo-second-order model and Langmuir model. Response surface methodology (RSM) was employed to investigate the effects of F- concentration, pH, adsorbent dosage and temperature on the removal efficiency. Analysis of variance (ANOVA) was used to test the adequacy of the mathematical models. The Nonelectrostatic model of modified fly ash cenospheres adsorbing fluoride was built through the Generalized composite method, indicating that two inner-spherical complexes, ≡SF and ≡SOHF-, were formed in the adsorption process by means of the ligand exchange and surface complexation. Optimization of the adsorption conditions enabled the realization of the practical needs for fluoride contaminated water.

Identification of Key Aroma Compounds in Type I Sourdough-Based Chinese Steamed Bread: Application of Untargeted Metabolomics Analysisp.

Untargeted metabolomics is a valuable tool to analyze metabolite profiles or aroma fingerprints of different food products. However, less attention has been paid to determining the aroma characteristics of Chinese steamed breads (CSBs) by using this approach. The aim of this work was to evaluate the key aroma compounds and their potential generation pathway in Chinese steamed bread produced with type I sourdough by a metabolomics approach. Based on the aroma characteristics analysis, CSBs produced with type I sourdough and baker's yeast were clearly distinguishable by principal component analysis (PCA) scores plot. A total of 13 compounds in sourdough-based steamed breads were given the status of discriminant markers through the untargeted metabolomics analysis. According to the odor activity values (OAVs) of discriminant aroma markers, ethyl acetate (fruity), ethyl lactate (caramel-like), hexyl acetate (fruity), (E)-2-nonenal (fatty) and 2-pentylfuran (fruity) were validated as the key volatile compounds in the breads produced with type I sourdough as compared to the baker's yeast leavened steamed bread. The metabolite analysis in proofed dough indicated that esters are mainly generated by the reaction between acid and alcohol during steaming, and aldehydes are derived from the oxidation of palmitoleic acid and linoleic acid during proofing and steaming.

The inhibition mechanism of ϵ-polylysine against Bacillus cereus emerging in surimi gel during refrigerated storage.

BACKGROUND: Refrigeration is commonly used in the processing and storage of surimi products. However, refrigerated surimi products are susceptible to microbial contamination, which leads to deterioration of the products and shortens their shelf life. The aims of the present study were therefore to evaluate the effects of ϵ-polylysine (ϵ-PL) on spoilage bacteria in surimi products, and to investigate the antibacterial mechanism of Bacillus cereus, which is the dominant spoilage bacterium. RESULTS: ϵ-Polylysine with a high degree of polymerization (20-30K) proved able to decrease the total number of colonies in surimi products and showed an obvious antibacterial effect against B. cereus. After ϵ-PL treatments, the distinct broken areas on the bacterial surfaces and the aggregations of cells were observed by scanning electron microscope (SEM). The intracellular materials, such as small molecules, soluble proteins, and deoxyribonucleic acids in the cells were analyzed, which revealed the destructive effects of ϵ-PL on bacterial cells. Experiments with propidium iodide (PI) infiltration experiments verified that the permeability of cell membranes was enhanced by ϵ-PL treatment. CONCLUSION: These results indicated that ϵ-PL could destroy the cell membranes and change the permeability of B. cereus, and subsequently the cell contents leaked out to achieve antibacterial effects. © 2018 Society of Chemical Industry.

Lactic Acid Bacteria as Antifungal and Anti-Mycotoxigenic Agents: A Comprehensive Review.

Fungal contamination of food and animal feed, especially by mycotoxigenic fungi, is not only a global food quality concern for food manufacturers, but it also poses serious health concerns because of the production of a variety of mycotoxins, some of which present considerable food safety challenges. In today's mega-scale food and feed productions, which involve a number of processing steps and the use of a variety of ingredients, fungal contamination is regarded as unavoidable, even good manufacturing practices are followed. Chemical preservatives, to some extent, are successful in retarding microbial growth and achieving considerably longer shelf-life. However, the increasing demand for clean label products requires manufacturers to find natural alternatives to replace chemically derived ingredients to guarantee the clean label. Lactic acid bacteria (LAB), with the status generally recognized as safe (GRAS), are apprehended as an apt choice to be used as natural preservatives in food and animal feed to control fungal growth and subsequent mycotoxin production. LAB species produce a vast spectrum of antifungal metabolites to inhibit fungal growth; and also have the capacity to adsorb, degrade, or detoxify fungal mycotoxins including ochratoxins, aflatoxins, and Fusarium toxins. The potential of many LAB species to circumvent spoilage associated with fungi has been exploited in a variety of human food and animal feed stuff. This review provides the most recent updates on the ability of LAB to serve as antifungal and anti-mycotoxigenic agents. In addition, some recent trends of the use of LAB as biopreservative agents against fungal growth and mycotoxin production are highlighted.

Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly.

Histone acetyltransferases and histone deacetylases (HDACs) are important epigenetic coregulators. It has been thought that HDACs associate with corepressor complexes and repress gene transcription; however, in this study, we have found that PU.1-a key master regulator for hematopoietic self-renewal and lineage specification-requires HDAC activity for gene activation. Deregulated PU.1 gene expression is linked to dysregulated hematopoiesis and the development of leukemia. In this study, we used erythroid differentiation as a model to analyze how the PU.1 gene is regulated. We found that active HDAC1 is directly recruited to active PU.1 promoter in progenitor cells, whereas acetylated HDAC1, which is inactive, is on the silenced PU.1 promoter in differentiated erythroid cells. We then studied the mechanism of HDAC1-mediated activation. We discovered that HDAC1 activates PU.1 gene transcription via deacetylation of TATA-binding protein-associated factor 9 (TAF9), a component in the transcription factor IID (TFIID) complex. Treatment with HDAC inhibitor results in an increase in TAF9 acetylation. Acetylated TAF9 does not bind to the PU.1 gene promoter and subsequently leads to the disassociation of the TFIID complex and transcription repression. Thus, these results demonstrate a key role for HDAC1 in PU.1 gene transcription and, more importantly, uncover a novel mechanism of TFIID recruitment and gene activation.-Jian, W., Yan, B., Huang, S., Qiu, Y. Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly.