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
N1 - Funding Information:
Much of the research reviewed in this paper was funded by the New Zealand Cross Departmental Research Programme andtheMinistry ofAgriculture andForestry under the Pathogen Transmission Routes Research Program chaired by Phil Journeaux (MAF, Hamilton).
Funding Information:
The potential sources of faecal contamination of freshwaters are diverse and can include point source discharges of wastewater from sewage treatment and animal processing plants, and contamination by domestic and feral animals (Ferguson et al. 2003). grazing livestock are considered to be the dominant source of faecal contamination to New Zealand's freshwaters (wilcock et al. 1999, 2006; donnison et al. 2004; Parliamentary Commissioner for the environment 2004). a s a consequence, the consortium-based Pathogen Transmission Routes Research Program (PTRRP) was established with funding from the New Zealand Cross departmental Research Programme and Ministry of agriculture and Forestry to (i) quantify the relative significance of key pathogen transmission routes from farm animals to water bodies, and (ii) identify and evaluate on-farm measures with which to mitigate faecal contamination.
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
UR - http://www.scopus.com/inward/record.url?scp=84881287607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881287607&partnerID=8YFLogxK
U2 - 10.1128/MCB.00145-13
DO - 10.1128/MCB.00145-13
M3 - Article
C2 - 23754746
AN - SCOPUS:84881287607
VL - 33
SP - 3150
EP - 3165
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 16
ER -