Epigenetic functions of smchd1 repress gene clusters on the inactive x chromosome and on autosomes

Anne Valerie Gendrel, Y. Amy Tang, Masako Suzuki, Jonathan Godwin, Tatyana B. Nesterova, John M. Greally, Edith Heard, Neil Brockdorff

Research output: Contribution to journalArticle

51 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3150-3165
Number of pages16
JournalMolecular and Cellular Biology
Volume33
Issue number16
DOIs
StatePublished - 2013

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Multigene Family
Epigenomics
Chromosomes
CpG Islands
Methylation
Genes
Prader-Willi Syndrome
Chromosomes, Human, Pair 7
Gene Expression Regulation
X Chromosome
Proteins
Genome
Brain

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 journalArticle

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. In: Molecular and Cellular Biology. 2013 ; Vol. 33, No. 16. pp. 3150-3165.
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