SmcHD1 underlies the formation of H3K9me3 blocks on the inactive X chromosome in mice [RNA-seq]
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PROVIDER: PRJNA828616 | ENA |
REPOSITORIES: ENA
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Project description:Stable silencing of the inactive X chromosome (Xi) in female mammals is crucial for the development of embryos and their postnatal health. SmcHD1 is essential for stable silencing of the Xi, and its functional deficiency results in derepression of many X-inactivated genes. Although SmcHD1 has been suggested to play an important role in the formation of higher-order chromatin structure of the Xi, the underlying mechanism is largely unknown. Here, we explore the epigenetic state of the Xi in SmcHD1-deficient epiblast stem cells and mouse embryonic fibroblasts in comparison with their wild-type counterparts. The results suggest that SmcHD1 underlies the formation of H3K9me3-enriched blocks on the Xi, which, although the importance of H3K9me3 has been largely overlooked in mice, play a crucial role in the establishment of the stably silenced state. We propose that the H3K9me3 blocks formed on the Xi facilitate robust heterochromatin formation in combination with H3K27me3, and that the substantial loss of H3K9me3 caused by SmcHD1 deficiency leads to aberrant distribution of H3K27me3 on the Xi and derepression of X-inactivated genes.
2022-07-20 | GSE201188 | GEO
Project description:Stable silencing of the inactive X chromosome (Xi) in female mammals is crucial for the development of embryos and their postnatal health. SmcHD1 is essential for stable silencing of the Xi, and its functional deficiency results in derepression of many X-inactivated genes. Although SmcHD1 has been suggested to play an important role in the formation of higher-order chromatin structure of the Xi, the underlying mechanism is largely unknown. Here, we explore the epigenetic state of the Xi in SmcHD1-deficient epiblast stem cells and mouse embryonic fibroblasts in comparison with their wild-type counterparts. The results suggest that SmcHD1 underlies the formation of H3K9me3-enriched blocks on the Xi, which, although the importance of H3K9me3 has been largely overlooked in mice, play a crucial role in the establishment of the stably silenced state. We propose that the H3K9me3 blocks formed on the Xi facilitate robust heterochromatin formation in combination with H3K27me3, and that the substantial loss of H3K9me3 caused by SmcHD1 deficiency leads to aberrant distribution of H3K27me3 on the Xi and derepression of X-inactivated genes.
2022-07-20 | GSE201187 | GEO
Project description:SmcHD1 underlies the formation of H3K9me3 blocks on the inactive X chromosome in mice
| PRJNA828613 | ENA
Project description:SmcHD1 underlies the formation of H3K9me3 blocks on the inactive X chromosome in mice [ChIP-seq]
| PRJNA828617 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-07-20 | GSE201189 | GEO
Project description:X chromosome inactivation involves multiple levels of chromatin modification, established progressively and in a stepwise manner during early development. The chromosomal protein Smchd1 has recently been shown to play an important role in DNA methylation of CpG islands (CGIs), a late step in the X inactivation pathway required for long-term stability of gene silencing. Here we show that inactive X chromosome (Xi) CGI methylation can occur via either Smchd1 dependent or independent pathways. Smchd1 dependent CGI methylation, the primary pathway, is acquired gradually over an extended period, whereas Smchd1 independent CGI methylation occurs rapidly after the onset of X inactivation. The de novo methyltransferase Dnmt3b is required for methylation of both classes of CGI, whereas Dnmt3a and Dnmt3L are dispensable. Xi CGIs methylated by these distinct pathways differ in respect to their sequence characteristics and immediate chromosomal environment. We discuss the implications of these results for understanding CGI methylation during development. Examination of CpG methylated DNA from wild type and smchd1 null male and female somatic cells and female ES cells differentiated for either 7 or 10 days. Duplicate samples of each type were generated.
2012-10-15 | E-GEOD-37333 | biostudies-arrayexpress
Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loc. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.
2018-06-30 | GSE111721 | GEO
Project description:X chromosome inactivation involves multiple levels of chromatin modification, established progressively and in a stepwise manner during early development. The chromosomal protein Smchd1 has recently been shown to play an important role in DNA methylation of CpG islands (CGIs), a late step in the X inactivation pathway required for long-term stability of gene silencing. Here we show that inactive X chromosome (Xi) CGI methylation can occur via either Smchd1 dependent or independent pathways. Smchd1 dependent CGI methylation, the primary pathway, is acquired gradually over an extended period, whereas Smchd1 independent CGI methylation occurs rapidly after the onset of X inactivation. The de novo methyltransferase Dnmt3b is required for methylation of both classes of CGI, whereas Dnmt3a and Dnmt3L are dispensable. Xi CGIs methylated by these distinct pathways differ in respect to their sequence characteristics and immediate chromosomal environment. We discuss the implications of these results for understanding CGI methylation during development.
2012-10-15 | GSE37333 | GEO
Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loci. Smchd1 deletion in differentiating ES cells results in failed Hox gene silencing. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.
2018-06-30 | GSE111724 | GEO
Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loc. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.
2018-06-30 | GSE115932 | GEO