SmcHD1 underlies the formation of H3K9me3 blocks on the inactive X chromosome in mice [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA828616 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18841978_1.fastq.gz | Fastqsanger.gz | |||
| SRR18841978_2.fastq.gz | Fastqsanger.gz | |||
| SRR18841979_1.fastq.gz | Fastqsanger.gz | |||
| SRR18841979_2.fastq.gz | Fastqsanger.gz | |||
| SRR18841980_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
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:Structural Maintenance of Chromosomes flexible Hinge Domain containing 1 (SMCHD1) is an SMC-like protein that plays an important role in X chromosome inactivation and is mutated in two human diseases, a muscular dystrophy, and a rare developmental disorder. Here we characterized the function of SMCHD1 in human myoblasts and focused on its role on autosomes. We found that SMCHD1 colocalizes with Lamin B1 and the constitutive heterochromatin mark H3K9me3. Loss of SMCHD1 leads to a loss of heterochromatin at nuclear lamina regions and to extensive changes of the epigenome on most chromosomes. In SMCHD1-deficient cells, about half the regions that normally bind SMCHD1 loose H3K9me3, acquire long stretches of DNA hypermethylation and gain a variety of active chromatin marks including H3K4me3, H3K4me1, histone H3K27 acetylation, and H3K36 di- and trimethylation. Three-dimensional chromatin analysis using HiC shows that long range contacts between different heterochromatin blocks (B compartments) on the same chromosome are diminished while there is extensive formation of new topologically associated domains (TADs) and loops anchored at newly created CTCF/RAD21 binding sites. Inactivation of SMCHD1 promotes many inactive (B) to active (A) compartment transitions. These transitions are accompanied by activation of about 200 previously silenced genes with potential implications for the etiology and progression of SMCHD1-linked diseases. Our data suggest that SMCHD1 functions as a genome compartment organizer and as an important anchor for heterochromatin domains at the nuclear lamina ensuring that lamina- associated domains are protected from histone and DNA modification enzymes that typically operate in active chromatin.
2025-06-27 | GSE251749 | GEO
Project description:Structural Maintenance of Chromosomes flexible Hinge Domain containing 1 (SMCHD1) is an SMC-like protein that plays an important role in X chromosome inactivation and is mutated in two human diseases, a muscular dystrophy, and a rare developmental disorder. Here we characterized the function of SMCHD1 in human myoblasts and focused on its role on autosomes. We found that SMCHD1 colocalizes with Lamin B1 and the constitutive heterochromatin mark H3K9me3. Loss of SMCHD1 leads to a loss of heterochromatin at nuclear lamina regions and to extensive changes of the epigenome on most chromosomes. In SMCHD1-deficient cells, about half the regions that normally bind SMCHD1 loose H3K9me3, acquire long stretches of DNA hypermethylation and gain a variety of active chromatin marks including H3K4me3, H3K4me1, histone H3K27 acetylation, and H3K36 di- and trimethylation. Three-dimensional chromatin analysis using HiC shows that long range contacts between different heterochromatin blocks (B compartments) on the same chromosome are diminished while there is extensive formation of new topologically associated domains (TADs) and loops anchored at newly created CTCF/RAD21 binding sites. Inactivation of SMCHD1 promotes many inactive (B) to active (A) compartment transitions. These transitions are accompanied by activation of about 200 previously silenced genes with potential implications for the etiology and progression of SMCHD1-linked diseases. Our data suggest that SMCHD1 functions as a genome compartment organizer and as an important anchor for heterochromatin domains at the nuclear lamina ensuring that lamina- associated domains are protected from histone and DNA modification enzymes that typically operate in active chromatin.
2025-06-27 | GSE251751 | 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:Structural Maintenance of Chromosomes flexible Hinge Domain containing 1 (SMCHD1) is an SMC-like protein that plays an important role in X chromosome inactivation and is mutated in two human diseases, a muscular dystrophy, and a rare developmental disorder. Here we characterized the function of SMCHD1 in human myoblasts and focused on its role on autosomes. We found that SMCHD1 colocalizes with Lamin B1 and the constitutive heterochromatin mark H3K9me3. Loss of SMCHD1 leads to a loss of heterochromatin at nuclear lamina regions and to extensive changes of the epigenome on most chromosomes. In SMCHD1-deficient cells, about half the regions that normally bind SMCHD1 loose H3K9me3, acquire long stretches of DNA hypermethylation and gain a variety of active chromatin marks including H3K4me3, H3K4me1, histone H3K27 acetylation, and H3K36 di- and trimethylation. Three-dimensional chromatin analysis using HiC shows that long range contacts between different heterochromatin blocks (B compartments) on the same chromosome are diminished while there is extensive formation of new topologically associated domains (TADs) and loops anchored at newly created CTCF/RAD21 binding sites. Inactivation of SMCHD1 promotes many inactive (B) to active (A) compartment transitions. These transitions are accompanied by activation of about 200 previously silenced genes with potential implications for the etiology and progression of SMCHD1-linked diseases. Our data suggest that SMCHD1 functions as a genome compartment organizer and as an important anchor for heterochromatin domains at the nuclear lamina ensuring that lamina- associated domains are protected from histone and DNA modification enzymes that typically operate in active chromatin.
2025-06-27 | GSE251750 | GEO
Project description:Structural Maintenance of Chromosomes flexible Hinge Domain containing 1 (SMCHD1) is an SMC-like protein that plays an important role in X chromosome inactivation and is mutated in two human diseases, a muscular dystrophy, and a rare developmental disorder. Here we characterized the function of SMCHD1 in human myoblasts and focused on its role on autosomes. We found that SMCHD1 colocalizes with Lamin B1 and the constitutive heterochromatin mark H3K9me3. Loss of SMCHD1 leads to a loss of heterochromatin at nuclear lamina regions and to extensive changes of the epigenome on most chromosomes. In SMCHD1-deficient cells, about half the regions that normally bind SMCHD1 loose H3K9me3, acquire long stretches of DNA hypermethylation and gain a variety of active chromatin marks including H3K4me3, H3K4me1, histone H3K27 acetylation, and H3K36 di- and trimethylation. Three-dimensional chromatin analysis using HiC shows that long range contacts between different heterochromatin blocks (B compartments) on the same chromosome are diminished while there is extensive formation of new topologically associated domains (TADs) and loops anchored at newly created CTCF/RAD21 binding sites. Inactivation of SMCHD1 promotes many inactive (B) to active (A) compartment transitions. These transitions are accompanied by activation of about 200 previously silenced genes with potential implications for the etiology and progression of SMCHD1-linked diseases. Our data suggest that SMCHD1 functions as a genome compartment organizer and as an important anchor for heterochromatin domains at the nuclear lamina ensuring that lamina- associated domains are protected from histone and DNA modification enzymes that typically operate in active chromatin.
2025-06-27 | GSE251748 | GEO