Genome-wide distribution of KAT6B and H3K23ac in mouse embryonic stem cells
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PROVIDER: PRJNA956936 | ENA |
REPOSITORIES: ENA
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Project description:Promoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying one of the two marks. These so-called bivalent domains are thought to poise genes for timely activation upon differentiation. Here we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, despite presence of H3K4me3, thereby promoting a poised state. Strikingly, the bivalent mark combination further promotes binding of chromatin proteins that are not recruited by each mark individually, including the histone acetyltransferase complex KAT6B (MORF). Knockout of KAT6B blocks neuronal differentiation, demonstrating that bivalency-specific readers are critical for proper ESC differentiation. These findings reveal how histone mark bivalency directly promotes establishment of a poised state at developmental genes, while highlighting how nucleosomal asymmetry is critical for histone mark readout and function.
2024-12-27 | GSE229987 | GEO
Project description:Heterozygous mutations in the histone acetyltransferase gene KAT6B (MYST4/MORF/QKF) cause cognitive disorders. Congruently, KAT6B is required for brain development, neural stem cell self-renewal and neuronal differentiation in mice. Despite the clear requirement for KAT6B in brain development, its molecular roles remain unexplored. Here we use CUT&Tag sequencing to determine the effects of loss or gain of KAT6B on H3K9ac and H3K23ac histone marks and on RNA Pol II.
2024-11-06 | GSE267672 | GEO
Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in forebrain neural stem and progenitor cells (NSPCs). We isolated NSPCs from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, from mouse embryos that lacked KAT6B or overexpressed KAT6B. We cultured the cells in vitro for 3 to 5 passages before isolating RNA for library production and RNA-sequencing. We found that genes required for neuronal differentiation and brain development were downregulated in Kat6b null cells and upregulated in Kat6b transgenic overexpressing cells.
2024-11-06 | GSE280783 | GEO
Project description:Epigenetic effects (H3K9ac, H3K14ac, H3K23ac and Pol II) of Kat6b loss in mouse neural stem cells (CUT&Tag)
| PRJNA1112385 | ENA
Project description:The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing haematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the haematopoietic system. We found that KAT6B sustained the fetal haematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished haematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating haematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg and Flt3. In conclusion, we identified the haematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.
2024-02-25 | GSE256039 | GEO
Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in the developing cerebral cortex. We isolated RNA from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, and from the E15.5 foetal cortex of mouse embryos and foetuses that lacked KAT6B or overexpressed KAT6B. Genes required for brain development and neuronal differentiation were downregulated in Kat6b null tissues and upregulated in Kat6b transgenic overexpressing tissue.
2024-11-06 | GSE280784 | GEO
Project description:We report genome-wide distribution of O-GlcNAcylated H2A at serine 40 (H2AS40Gc) in mouse embryonic stem cells (mESCs, J1 line) cultured in 25 mM glucose (HG-mESCs) or 1 mM glucose (LG-mESCs) condition. We found that H2AS40Gc was mainly located at genic area, positively correlated with the gene expression both in HG- and LG-mESCs. Interestingly, H2AS40Gc localization was overlapped with H2AX, γH2AX and O-GlcNAc transferase (Ogt), and varied by extracellular glucose concentration. This study using ChIP-seq and RNA-seq analysis provides genomic distribution of newly O-GlcNAc histone modification in mESCs.
2020-02-02 | GSE77999 | GEO
Project description:Circular RNA has been reported to be dynamically expressed during embryonic development and regulates human embryonic stem cells (hESCs), but the identification and regulation of functional circular RNA in mouse embryonic stem cells (mESC) remains unclear. Here we found over 1,000 circular RNAs in different mESC states. One of these, circular RNA Kat6b-exon2 (circKat6b-e2), was significantly overexpressed in mESCs. Furthermore, short-hair RNA (shRNA) mediated knockdown of circKat6b-e2 expression significantly inhibited mESC self-renewal and EB differentiation. The transcriptome also revealed that circKat6b-e2 is required to ensure the differentiation of the mESC lineage. Finally, we also found that more Alu elements surrounding circKat6b-e2 were necessary factors for its expression. Conclusions: our study shows that Alu element-dependent expression of circKat6b-e2 mediates mESC self-renewal and lineage differentiation.
2022-08-28 | GSE211667 | GEO
Project description:To develop our gene expression experiment, we have employed whole genome microarray expression profiling as a discovery platform to identify genes potentially regulated by the transcriptional coactivator KAT6B. Expression of KAT6B gene was downregulated in two human SCLC cell lines using two different short hairpin RNAs. RNAs from these modified cell lines were hybridized in Agilent platform.
2015-10-07 | GSE59136 | GEO
Project description:modENCODE_submission_2997 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Developmental Stage: Embryo 14-16hr OR; Genotype: wild type; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Antibody H3K23ac (target is H3K23ac); Developmental Stage Embryo 14-16hr OR
2011-10-12 | E-GEOD-32734 | biostudies-arrayexpress