Lsh controls Hox gene silencing during development.
Polycomb-mediated repression and DNA methylation are important epigenetic mechanisms of gene silencing. Recent evidence suggests a functional link between the polycomb repressive complex (PRC) and Dnmts in cancer cells. Here we provide evidence that Lsh, a regulator of DNA methylation, is also involved in normal control of PRC-mediated silencing during embryogenesis. We demonstrate that Lsh, a SNF2 homolog, can associate with some Hox genes and regulates Dnmt3b binding, DNA methylation, and silencing of Hox genes during development. Moreover, Lsh can associate with PRC1 components and influence PRC-mediated histone modifications. Thus Lsh is part of a physiological feedback loop that reinforces DNA methylation and silencing of PRC targets.
Xi
Sichuan
S
Laboratory of Cancer Prevention, SAIC-Frederick, National Cancer Institute, Frederick, MD 21702-1201, USA.
Zhu
Heming
H
Xu
Hong
H
Schmidtmann
Anja
A
Geiman
Theresa M
TM
Muegge
Kathrin
K
D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism
D018398:Homeodomain Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D004265:DNA Helicases; C491758:lymphoid specific helicase, mouse