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Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes

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 gen...

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Autores principales: Gendrel, Anne-Valerie, Tang, Y. Amy, Suzuki, Masako, Godwin, Jonathan, Nesterova, Tatyana B., Greally, John M., Heard, Edith, Brockdorff, Neil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753908/
https://www.ncbi.nlm.nih.gov/pubmed/23754746
http://dx.doi.org/10.1128/MCB.00145-13
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author Gendrel, Anne-Valerie
Tang, Y. Amy
Suzuki, Masako
Godwin, Jonathan
Nesterova, Tatyana B.
Greally, John M.
Heard, Edith
Brockdorff, Neil
author_facet Gendrel, Anne-Valerie
Tang, Y. Amy
Suzuki, Masako
Godwin, Jonathan
Nesterova, Tatyana B.
Greally, John M.
Heard, Edith
Brockdorff, Neil
author_sort Gendrel, Anne-Valerie
collection PubMed
description 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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spelling pubmed-37539082013-09-03 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 Mol Cell Biol Articles 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. American Society for Microbiology 2013-08 /pmc/articles/PMC3753908/ /pubmed/23754746 http://dx.doi.org/10.1128/MCB.00145-13 Text en Copyright © 2013, Gendrel et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Articles
Gendrel, Anne-Valerie
Tang, Y. Amy
Suzuki, Masako
Godwin, Jonathan
Nesterova, Tatyana B.
Greally, John M.
Heard, Edith
Brockdorff, Neil
Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes
title Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes
title_full Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes
title_fullStr Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes
title_full_unstemmed Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes
title_short Epigenetic Functions of Smchd1 Repress Gene Clusters on the Inactive X Chromosome and on Autosomes
title_sort epigenetic functions of smchd1 repress gene clusters on the inactive x chromosome and on autosomes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753908/
https://www.ncbi.nlm.nih.gov/pubmed/23754746
http://dx.doi.org/10.1128/MCB.00145-13
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