Open AccessLsh Participates in DNA Methylation and Silencing of Stem Cell Genes
Author(s) -
Xi Sichuan,
Geiman Theresa M.,
Briones Victorino,
Guang Tao Yong,
Xu Hong,
Muegge Kathrin
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.183
Subject(s) - biology , stem cell , dna methylation , reprogramming , epigenetics , cell potency , embryonic stem cell , gene silencing , cellular differentiation , microbiology and biotechnology , chromatin , adult stem cell , genetics , gene , gene expression
Transcriptional control of stem cell genes is a critical step in differentiation of embryonic stem cells and in reprogramming of somatic cells into stem cells. Here we report that Lsh, a regulator of repressive chromatin at retrotransposons, also plays an important role in silencing of stem cell‐specific genes such as Oct4. We found that CpG methylation is gained during in vitro differentiation of several stem cell‐specific genes (in 11 of 12 promoter regions) and thus appears to be a common epigenetic mark. Lsh depletion prevents complete silencing of stem cell gene expression and moreover promotes the maintenance of stem cell characteristics in culture. Lsh is required for establishment of DNA methylation patterns at stem cell genes during differentiation, in part by regulating access of Dnmt3b to its genomic targets. Our results indicate that Lsh is involved in the control of stem cell genes and suggest that Lsh is an important epigenetic modulator during early stem cell differentiation. S TEM C ELLS 2009;27:2691–2702