The unique establishment of histone H3 lysine 4 mono-methylation pattern on the promoter regions in early embryo development [RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE179939 | GEO | 2022/07/10
REPOSITORIES: GEO
Similar Datasets
Project description:Histone H3 lysine 4 methylation on promoter regions plays essential roles in transcriptional regulation in mouse early embryo development. Here, we presented the first genome-wide map of H3K4me1 in mouse pre-implantation embryos and observed a unique establishment process of H3K4me1 pattern on promoter regions, which is strongly correlated with active transcription and the broad H3K4me3 domain formation. We further demonstrate that the histone methyltransferase ASH2L contributes to forming the H3K4me1 DIP pattern on the promoter regions in mouse pre-implantation embryos.
2022-07-10 | GSE179937 | GEO
Project description:10% of methylation sites in CpG islands. In this study, the genome-wide CpG islands of human sperm, oocyte and pre-implantation embryos were analyzed using the almost complete coverage of promoters and CpG islands (most methylation-producing regions) methylation microarray method (MeDIP-Chip). Dynamic changes in methylation of sub-regions to understand the dynamic pattern of CpG island and promoter methylation, possible regulatory mechanisms of this methylation dynamic change, and function during early embryonic development.
2020-02-01 | GSE124358 | GEO
Project description:Cell fate decisions are closely associated with changes in gene expression programs. A large number of post-translational modifications of core histones contribute to controlling the expression of genes. A modification that is closely correlated with open chromatin and gene transcription is methylation of lysine 4 of histone H3 (H3K4). It is catalyzed by methyltransferases of the KMT2 family, which require interaction with 4 core subunits, WDR5, RBBP5, ASH2L and DPY30, for catalytic activity. Ash2l is required for organismal development and for tissue homeostasis in the mouse. In mouse embryo fibroblasts (MEFs), the loss of Ash2l results in downregulated gene expression, which provokes a senescence phenotype. We now find that both H3K4 mono- and tri-methylation (H3K4me1 and me3, respectively) are deregulated. H3K4me3 is lost while H3K4me1 is increased at promoters upon knockout of Ash2l. In particular, loss of H3K4me3 at promoters correlates with downregulation of gene expression, which is particularly obvious at CpG island promoters. Ash2l loss results in an increase of histone H3 loading at promoters, paralleled by enhanced chromatin compaction. This is accompanied by an increase of repressing and a decrease of activating histone marks. One of the sequence-specific transcription factors with altered binding upon depletion of Ash2l is CTCF. It is lost from some promoter-associated sites, but gained binding in other regions of the genome. This suggests that in addition to the well-known effects on H3K4 methylation upon depleting KMT2 complex components, Ash2l loss affects chromatin compaction. Whether the decrease of H3K4me3 promotes chromatin compaction at promoters or whether these are independent consequences of Ash2l loss remains to be determined. We suggest that both contribute mechanistically to gene repression and thus to the observed cellular effects.
2022-12-13 | GSE205232 | GEO
Project description:Cell fate decisions are closely associated with changes in gene expression programs. A large number of post-translational modifications of core histones contribute to controlling the expression of genes. A modification that is closely correlated with open chromatin and gene transcription is methylation of lysine 4 of histone H3 (H3K4). It is catalyzed by methyltransferases of the KMT2 family, which require interaction with 4 core subunits, WDR5, RBBP5, ASH2L and DPY30, for catalytic activity. Ash2l is required for organismal development and for tissue homeostasis in the mouse. In mouse embryo fibroblasts (MEFs), the loss of Ash2l results in downregulated gene expression, which provokes a senescence phenotype. We now find that both H3K4 mono- and tri-methylation (H3K4me1 and me3, respectively) are deregulated. H3K4me3 is lost while H3K4me1 is increased at promoters upon knockout of Ash2l. In particular, loss of H3K4me3 at promoters correlates with downregulation of gene expression, which is particularly obvious at CpG island promoters. Ash2l loss results in an increase of histone H3 loading at promoters, paralleled by enhanced chromatin compaction. This is accompanied by an increase of repressing and a decrease of activating histone marks. One of the sequence-specific transcription factors with altered binding upon depletion of Ash2l is CTCF. It is lost from some promoter-associated sites, but gained binding in other regions of the genome. This suggests that in addition to the well-known effects on H3K4 methylation upon depleting KMT2 complex components, Ash2l loss affects chromatin compaction. Whether the decrease of H3K4me3 promotes chromatin compaction at promoters or whether these are independent consequences of Ash2l loss remains to be determined. We suggest that both contribute mechanistically to gene repression and thus to the observed cellular effects.
2022-12-13 | GSE205231 | GEO
Project description:Cell fate decisions are closely associated with changes in gene expression programs. A large number of post-translational modifications of core histones contribute to controlling the expression of genes. A modification that is closely correlated with open chromatin and gene transcription is methylation of lysine 4 of histone H3 (H3K4). It is catalyzed by methyltransferases of the KMT2 family, which require interaction with 4 core subunits, WDR5, RBBP5, ASH2L and DPY30, for catalytic activity. Ash2l is required for organismal development and for tissue homeostasis in the mouse. In mouse embryo fibroblasts (MEFs), the loss of Ash2l results in downregulated gene expression, which provokes a senescence phenotype. We now find that both H3K4 mono- and tri-methylation (H3K4me1 and me3, respectively) are deregulated. H3K4me3 is lost while H3K4me1 is increased at promoters upon knockout of Ash2l. In particular, loss of H3K4me3 at promoters correlates with downregulation of gene expression, which is particularly obvious at CpG island promoters. Ash2l loss results in an increase of histone H3 loading at promoters, paralleled by enhanced chromatin compaction. This is accompanied by an increase of repressing and a decrease of activating histone marks. One of the sequence-specific transcription factors with altered binding upon depletion of Ash2l is CTCF. It is lost from some promoter-associated sites, but gained binding in other regions of the genome. This suggests that in addition to the well-known effects on H3K4 methylation upon depleting KMT2 complex components, Ash2l loss affects chromatin compaction. Whether the decrease of H3K4me3 promotes chromatin compaction at promoters or whether these are independent consequences of Ash2l loss remains to be determined. We suggest that both contribute mechanistically to gene repression and thus to the observed cellular effects.
2022-12-13 | GSE205230 | GEO
Project description:FOXA1 is a pioneer factor that is important in hormone dependent cancer cells to stabilise nuclear receptors, such as estrogen receptor (ER) to chromatin. FOXA1 binds to enhancers regions that are enriched in H3K4mono- and dimethylation (H3K4me1, H3K4me2) histone marks and evidence suggests that these marks are requisite events for FOXA1 to associate with enhancers to initate subsequent gene expression events. However, exogenous expression of FOXA1 has been shown to induce H3K4me1 and H3K4me2 signal at enhancer elements and the order of events and the functional importance of these events is not clear. We performed a FOXA1 Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells in order to identify FOXA1 interacting partners and we found histone-lysine N-methyltransferase (MLL3) as the top FOXA1 interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition, in line with our observation that MLL3 associates with an enhancer specific protein. We performed MLL3 ChIP-seq in breast cancer cells and unexpectedly found that MLL3 binds mostly at non-promoter regions enhancers, in contrast to the prevailing hypothesis. MLL3 was shown to occupy regions marked by FOXA1 occupancy and as expected, H3K4me1 and H3K4me2. MLL3 binding was dependent on FOXA1, indicating that FOXA1 recruits MLL3 to chromatin. Motif analysis and subsequent genomic mapping revealed a role for Grainy head like protein-2 (GRHL2) which was shown to co-occupy regions of the chromatin with MLL3. Regions occupied by all three factors, namely FOXA1, MLL3 and GRHL2, were most enriched in H3K4me1. MLL3 silencing decreased H3K4me1 at enhancer elements, but had no appreciable impact on H3K4me3 at enhancer elements. We identify a complex relationship between FOXA1, MLL3 and H3K4me1 at enhancers in breast cancer and propose a mechanism whereby the pioneer factor FOXA1 can interact with a chromatin modifier MLL3, recruiting it to chromatin to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements.
2016-12-12 | PXD005253 | Pride
Project description:The trithorax protein ASH2L is essential for organismal and tissue development and for cell proliferation. ASH2L is a subunit of KMT2/COMPASS methyltransferase complexes that catalyze the methylation of histone H3 lysine 4 (H3K4). Tri- and mono-methylation of H3K4 (H3K4me1 and H3K4me1) are associated with active promoters and enhancers, respectively. The molecular relevance of these modifications is not fully understood. We have used mouse embryo cells with a PROTAC-sensitive, degradable ASH2L to assess the functional consequences of KMT2 complex inactivation. The rapid loss of ASH2L resulted in a sequential alterations of histone marks at promoters, first a decrease of H3K4me1, then an increase of H3K4me1, and a decrease of H3K27ac during the first 16 hrs, while an increase in H3K27me3 was very slow. These consequences were most prominent at CpG island promoters within a window of ±1 kb of the transcription start sites. Despite the the rapid loss of ASH2L, the effect on transcription in the first 8 hrs was minimal. This was accompanied with an alterations in gene expression and associated proliferation stop and cell cycle arrest. These findings suggest an order series of events upon loss of ASH2L that requires considerable amount of time to unfold.
2023-09-12 | GSE240992 | GEO
Project description:Lima1 is an extensively studied prognostic marker of malignancy and is also considered to be a tumour suppressor, but its role in a developmental context of non-transformed cells is poorly understood. Here, we characterised the expression pattern and examined the function of Lima1 in mouse embryos and pluripotent stem cell lines. We found that Lima1 expression is controlled by the naïve pluripotency circuit and is required for the suppression of membrane blebbing. Moreover, Lima1 is essential for proper mitochondrial energetics, which is crucial for the growth of solid tumours. Forcing Lima1 expression enabled human pluripotent stem cells to be incorporated into murine pre-implantation embryos, trespassing the interspecies engraftment barrier. Thus, Lima1 is a key effector molecule that mediates the pluripotency control of membrane dynamics and cellular metabolism.
2021-12-16 | PXD025293 | Pride
Project description:Pluripotent stem cells provide a platform to interrogate control elements that function to generate all cell types of the body. Despite their utility for modeling development and disease, the relationship of mouse and human pluripotent stem cell states to one another remains largely undefined. We have shown that mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) are distinct, pluripotent states isolated from pre- and post-implantation embryos respectively. Human ES cells are different than mouse ES cells and share defining features with EpiSCs, yet are derived from pre-implantation human embryos. Here we show that EpiSCs can be routinely derived from pre-implantation mouse embryos. The pre-implantation-derived EpiSCs exhibit molecular features and functional properties consistent with bona fide EpiSCs. These results provide a simple method for isolating EpiSCs and offer direct insight into the intrinsic and extrinsic mechanisms that regulate the acquisition of distinct pluripotent states.
2011-01-25 | GSE26814 | GEO
Project description:Transcriptome analysis of pre-implantation embryos
| PRJNA937171 | ENA