Lsh Participates in DNA Methylation and Silencing of Stem Cell Genes

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‐spe...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2009-11, Vol.27 (11), p.2691-2702
Main Authors: Xi, Sichuan, Geiman, Theresa M., Briones, Victorino, Guang Tao, Yong, Xu, Hong, Muegge, Kathrin
Format: Article
Language:English
Subjects:
Animals
Blotting, Southern
Blotting, Western
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Line
Cell Line, Tumor
Chromatin
Chromatin Immunoprecipitation
Chromosomal Proteins, Non-Histone
Differentiation
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Helicases - genetics
DNA Helicases - metabolism
DNA Methylation
DNA Methyltransferase 3B
Epidermal Growth Factor - genetics
Epigenetics
Gene Silencing
Growth Differentiation Factor 3 - genetics
Homeodomain Proteins - genetics
Membrane Glycoproteins - genetics
Mice
Nanog Homeobox Protein
Neoplasm Proteins - genetics
Octamer Transcription Factor-3 - genetics
Polymerase Chain Reaction
Promoter Regions, Genetic - genetics
Protein Binding
Repressor Proteins - genetics
Stem cell genes
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Summary: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. STEM CELLS 2009;27:2691–2702
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.183