Abstract
The Smchd1 gene encodes a large protein with homology to the SMC family of proteins involved in chromosome condensation and cohesion. Previous studies have found that Smchd1 has an important role in CpG island (CGI) methylation on the inactive X chromosome (Xi) and in stable silencing of some Xi genes. In this study, using genome-wide expression analysis, we showed that Smchd1 is required for the silencing of around 10% of the genes on Xi, apparently independent of CGI hypomethylation, and, moreover, that these genes nonrandomly occur in clusters. Additionally, we found that Smchd1 is required for CpG island methylation and silencing at a cluster of four imprinted genes in the Prader-Willi syndrome (PWS) locus on chromosome 7 and genes from the protocadherin-alpha and -beta clusters. All of the affected autosomal loci display developmentally regulated brain-specific methylation patterns which are lost in Smchd1 homozygous mutants. We discuss the implications of these findings for understanding the function of Smchd1 in epigenetic regulation of gene expression
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3150-3165 |
| Number of pages | 16 |
| Journal | Molecular and Cellular Biology |
| Volume | 33 |
| Issue number | 16 |
| DOIs | |
| State | Published - 2013 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Epigenetic functions of smchd1 repress gene clusters on the inactive x chromosome and on autosomes. / Gendrel, Anne Valerie; Tang, Y. Amy; Suzuki, Masako; Godwin, Jonathan; Nesterova, Tatyana B.; Greally, John M.; Heard, Edith; Brockdorff, Neil.
In: Molecular and Cellular Biology, Vol. 33, No. 16, 2013, p. 3150-3165.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epigenetic functions of smchd1 repress gene clusters on the inactive x chromosome and on autosomes
AU - Gendrel, Anne Valerie
AU - Tang, Y. Amy
AU - Suzuki, Masako
AU - Godwin, Jonathan
AU - Nesterova, Tatyana B.
AU - Greally, John M.
AU - Heard, Edith
AU - Brockdorff, Neil
PY - 2013
Y1 - 2013
N2 - The Smchd1 gene encodes a large protein with homology to the SMC family of proteins involved in chromosome condensation and cohesion. Previous studies have found that Smchd1 has an important role in CpG island (CGI) methylation on the inactive X chromosome (Xi) and in stable silencing of some Xi genes. In this study, using genome-wide expression analysis, we showed that Smchd1 is required for the silencing of around 10% of the genes on Xi, apparently independent of CGI hypomethylation, and, moreover, that these genes nonrandomly occur in clusters. Additionally, we found that Smchd1 is required for CpG island methylation and silencing at a cluster of four imprinted genes in the Prader-Willi syndrome (PWS) locus on chromosome 7 and genes from the protocadherin-alpha and -beta clusters. All of the affected autosomal loci display developmentally regulated brain-specific methylation patterns which are lost in Smchd1 homozygous mutants. We discuss the implications of these findings for understanding the function of Smchd1 in epigenetic regulation of gene expression
AB - The Smchd1 gene encodes a large protein with homology to the SMC family of proteins involved in chromosome condensation and cohesion. Previous studies have found that Smchd1 has an important role in CpG island (CGI) methylation on the inactive X chromosome (Xi) and in stable silencing of some Xi genes. In this study, using genome-wide expression analysis, we showed that Smchd1 is required for the silencing of around 10% of the genes on Xi, apparently independent of CGI hypomethylation, and, moreover, that these genes nonrandomly occur in clusters. Additionally, we found that Smchd1 is required for CpG island methylation and silencing at a cluster of four imprinted genes in the Prader-Willi syndrome (PWS) locus on chromosome 7 and genes from the protocadherin-alpha and -beta clusters. All of the affected autosomal loci display developmentally regulated brain-specific methylation patterns which are lost in Smchd1 homozygous mutants. We discuss the implications of these findings for understanding the function of Smchd1 in epigenetic regulation of gene expression
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U2 - 10.1128/MCB.00145-13
DO - 10.1128/MCB.00145-13
M3 - Article
VL - 33
SP - 3150
EP - 3165
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 16
ER -