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Publication : Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation.

First Author  Gu B Year  2009
Journal  J Cell Biol Volume  185
Issue  5 Pages  811-26
PubMed ID  19487454 Mgi Jnum  J:163218
Mgi Id  MGI:4821247 Doi  10.1083/jcb.200810133
Citation  Gu B, et al. (2009) Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation. J Cell Biol 185(5):811-26
abstractText  Recent studies have unequivocally identified multipotent stem/progenitor cells in mammary glands, offering a tractable model system to unravel genetic and epigenetic regulation of epithelial stem/progenitor cell development and homeostasis. In this study, we show that Pygo2, a member of an evolutionarily conserved family of plant homeo domain-containing proteins, is expressed in embryonic and postnatal mammary progenitor cells. Pygo2 deficiency, which is achieved by complete or epithelia-specific gene ablation in mice, results in defective mammary morphogenesis and regeneration accompanied by severely compromised expansive self-renewal of epithelial progenitor cells. Pygo2 converges with Wnt/beta-catenin signaling on progenitor cell regulation and cell cycle gene expression, and loss of epithelial Pygo2 completely rescues beta-catenin-induced mammary outgrowth. We further describe a novel molecular function of Pygo2 that is required for mammary progenitor cell expansion, which is to facilitate K4 trimethylation of histone H3, both globally and at Wnt/beta-catenin target loci, via direct binding to K4-methyl histone H3 and recruiting histone H3 K4 methyltransferase complexes.
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