Lsh controls silencing of the imprinted Cdkn1c gene.
Epigenetic regulation, such as DNA methylation plays an important role in the control of imprinting. Lsh, a member of the SNF2 family of chromatin remodeling proteins, controls DNA methylation in mice. To investigate whether Lsh affects imprinting, we examined CpG methylation and allelic expression of individual genes in Lsh-deficient embryos. We report here that loss of Lsh specifically alters expression of the Cdkn1c gene (also known as p57(Kip2)) but does not interfere with maintenance of imprints at the H19, Igf2, Igf2r, Zac1 and Meg9 genes. The reactivation of the silenced paternal Cdkn1c allele correlates closely with a loss of CpG methylation at the 5' DMR at the Cdkn1c promoter, whereas KvDMR1 and DMRs of other imprinted genes were not significantly changed. Chromatin immunoprecipitations demonstrate a direct association of Lsh with the 5' DMR at the Cdkn1c promoter, but not with Kv DMR1 or other imprinted loci. These data suggest that methylation of the 5' DMR plays an important role in the imprinting of the Cdkn1c gene. Furthermore, it suggests that Lsh is not required for maintenance of imprinting marks in general, but is only crucial for imprinting at distinct genomic sites.
Fan
Tao
T
Laboratory of Molecular Immunoregulation, Basic Research Program, SAIC-Frederick, National Cancer Institute, Frederick, MD 21702-1201, USA.
Hagan
John P
JP
Kozlov
Serguei V
SV
Stewart
Colin L
CL
Muegge
Kathrin
K
D024506:5' Flanking Region; D000818:Animals; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004265:DNA Helicases / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D020868:Gene Silencing; D018392:Genomic Imprinting / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; D009687:Nuclear Proteins; D004265:DNA Helicases; C491758:lymphoid specific helicase, mouse