Characterization of the role of SETDB1 in Muscle stem cells during skeletal muscle regeneration [ChIP-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE253437 | GEO | 2024/03/23
REPOSITORIES: GEO
Similar Datasets
Project description:We are characterizing the rol of an H3K9 histone methyltransferase. As these proteins have the capacity to modulate chromatin, we investigate the chromatin modulation using ATAC-seq Muscle Stem Cells were isolated from the conditional mice model Setdb1-cKO and were isolated by Magnetic-activated cell sorting (MACS) and cultured in vitro
2024-03-23 | GSE233393 | GEO
Project description:Histones modulate gene expression by chromatin compaction, regulating numerous processes such as differentiation. However, the mechanisms underlying histone degradation remain elusive. When compared with their differentiated counterparts, immortal human embryonic stem cells (hESCs) have a unique chromatin architecture and low levels of trimethylated histone H3 at lysine 9 (H3K9me3), a heterochromatin-associated modification. Here we assess a link between the intrinsic epigenetic landscape and ubiquitin-proteasome system of hESCs. We find that hESCs exhibit high expression of UBE2K, a ubiquitin-conjugating enzyme. Loss of UBE2K increases the levels of H3K9 trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation. Concomitantly, loss of UBE2K impairs the ability of hESCs to differentiate into neural progenitors with neurogenic properties. Besides H3K9 trimethylation, we find that UBE2K binds histone H3 to induce its polyubiquitination and degradation by the proteasome. Notably, ubc-20, the worm orthologue of UBE2K, also regulates both histone H3 levels and H3K9 trimethylation in C. elegans germline. Thus, our results indicate that UBE2K crosses evolutionary boundaries to promote histone H3 degradation and reduce H3K9me3 repressive marks in immortal cells.
2020-06-01 | PXD018625 | Pride
Project description:Histones modulate gene expression by chromatin compaction, regulating numerous processes such as differentiation. However, the mechanisms underlying histone degradation remain elusive. When compared with their differentiated counterparts, immortal human embryonic stem cells (hESCs) have a unique chromatin architecture and low levels of trimethylated histone H3 at lysine 9 (H3K9me3), a heterochromatin-associated modification. Here we assess a link between the intrinsic epigenetic landscape and ubiquitin-proteasome system of hESCs. We find that hESCs exhibit high expression of UBE2K, a ubiquitin-conjugating enzyme. Loss of UBE2K increases the levels of H3K9 trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation. Concomitantly, loss of UBE2K impairs the ability of hESCs to differentiate into neural progenitors with neurogenic properties. Besides H3K9 trimethylation, we find that UBE2K binds histone H3 to induce its polyubiquitination and degradation by the proteasome. Notably, ubc-20, the worm orthologue of UBE2K, also regulates both histone H3 levels and H3K9 trimethylation in C. elegans germline. Thus, our results indicate that UBE2K crosses evolutionary boundaries to promote histone H3 degradation and reduce H3K9me3 repressive marks in immortal cells.
2020-06-01 | PXD018621 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-23 | GSE233396 | GEO
Project description:The histone 3 lysine 9 (H3K9)-specific methyltransferase (KMT) Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on Setdb1 role(s) in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation. Ex vivo studies on isolated single myofibres showed that Setdb1 is required for muscle adult stem cells expansion following activation and in vitro studies on skeletal myoblasts confirmed that Setdb1 suppresses terminal myoblast differentiation. We used genome-wide analyses to identify Setdb1 direct target genes in myoblasts and observed a release of Setdb1 from the promoter of selected target genes upon myoblast terminal differentiation, concomitant to a nuclear export of Setdb1 to the cytoplasm. We demonstrated that both genomic release and cytoplasmic Setdb1 relocalisation during differentiation were dependent on canonical Wnt signalling. Taken together, our findings uncover a functional link between Setdb1 and canonical Wnt signalling in skeletal muscle cells, which affects the expression of a subset of Setdb1 target genes. We revealed Wnt-dependent subcellular relocalisation of Setdb1 as a novel mechanism regulating Setdb1 functions. ChIP-seq of Setdb1 and H3K9me3 in Myoblast cells (C2C12)
2016-02-01 | E-GEOD-65493 | biostudies-arrayexpress
Project description:Muscle regeneration is process where different type of cells are interacting together to ensure a proper muscle regeneration. As Muscle stem cells are the central protagonist of muscle regeneration, we performed single cell RNA-seq to observe the change between the different cell types when SETDB1 is absent in Muscle stem cells.
2024-03-23 | GSE233395 | GEO
Project description:Muscle regeneration is process where different type of cells are interacting together to ensure a proper muscle regeneration. As Muscle stem cells are the central protagonist of muscle regeneration, we performed single cell RNA-seq to observe the change between the different cell types when SETDB1 is absent in Muscle stem cells. Muscle Stem Cells were isolated from the conditional mice model Setdb1-cKO and were isolated by Fluorescence-activated cell sorting (FACS).
2024-03-23 | GSE233394 | GEO
Project description:Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1 which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis. H3K4me3, H3K27me3, H3K9me3, SETDB1, MBD1, and Pol II ChIP-seq. m5CpG pull-down using recombinant MBD domain of MBD1 followed by next-generation sequencing.
2015-11-19 | E-GEOD-73432 | biostudies-arrayexpress
Project description:Post-translational modifications of histone tails play a crucial role in gene regulation. Here, we performed chromatin profiling by quantitative targeted mass spectrometry to assess all possible modifications of the core histones. We discovered a novel bivalent combination, a dually-marked H3K9me3/H3K14ac modification in the liver, that is significantly decreased in old hepatocytes. Subsequent genome-wide location analysis (ChIP-Seq) identified 1032 and 668 bivalent regions in young and old livers, respectively, with 280 in common. Histone H3K9 deacetylase Hdac3, as well as H3K9 methyltransferase Setdb1, found in complex Kap1, occupied bivalent regions in both young and old livers, correlating to presence of H3K9me3. Expression of genes associated with bivalent regions in young liver, including those regulating cholesterol secretion and triglyceride synthesis, is upregulated in old liver once the bivalency is lost. Hence, H3K9me3/H3K14ac dually-marked regions define a poised inactive state that is resolved with loss of one or both of the chromatin marks, which subsequently leads to change in gene expression.
2019-12-02 | GSE130712 | GEO
Project description:Transcription factors that play key roles in regulating embryonic stem (ES) cell state have been identified, but the chromatin regulators that help maintain ES cells are less well understood. A high-throughput shRNA screen was used to identify novel chromatin regulators that influence ES cell state. Loss of histone H3K9 methyltransferases, particularly SetDB1, had the most profound effects on ES cells. ChIP-Seq and functional analysis revealed that SetDB1 and histone H3K9 methylated nucleosomes occupy and repress genes encoding developmental regulators. These SetDB1-occupied genes are a subset of the M-bM-^@M-^\bivalentM-bM-^@M-^] genes, which contain nucleosomes with H3K4me3 and H3K27me3 modifications catalyzed by trithorax and polycomb group proteins, respectively. These genes are subjected to repression by both polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state. ChIP-seq data for SetDB1 and H3K9me3 in mouse ES cells.
2009-11-01 | E-GEOD-18371 | biostudies-arrayexpress