Pygo2 Expands Mammary Progenitor Cells by Facilitating Histone H3 K4 Methylation
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 evolution...
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| Veröffentlicht in: | The Journal of cell biology 2009-06, Vol.185 (5), p.811-826 |
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| creator | Gu, Bingnan Sun, Peng Yuan, Yuanyang Moraes, Ricardo C. Li, Aihua Teng, Andy Agrawal, Anshu Rhéaume, Catherine Bilanchone, Virginia Veltmaat, Jacqueline M. Takemaru, Ken-Ichi Millar, Sarah Lee, Eva Y.-H. P. Lewis, Michael T. Li, Boan Dai, Xing |
| description | 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. |
| doi_str_mv | 10.1083/jcb.200810133 |
| format | Article |
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P. ; Lewis, Michael T. ; Li, Boan ; Dai, Xing</creator><creatorcontrib>Gu, Bingnan ; Sun, Peng ; Yuan, Yuanyang ; Moraes, Ricardo C. ; Li, Aihua ; Teng, Andy ; Agrawal, Anshu ; Rhéaume, Catherine ; Bilanchone, Virginia ; Veltmaat, Jacqueline M. ; Takemaru, Ken-Ichi ; Millar, Sarah ; Lee, Eva Y.-H. P. ; Lewis, Michael T. ; Li, Boan ; Dai, Xing</creatorcontrib><description>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.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200810133</identifier><identifier>PMID: 19487454</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Animals ; beta Catenin - genetics ; beta Catenin - metabolism ; Breasts ; Cell Cycle ; Cell Proliferation ; Cells ; Chromatin ; Epithelial cells ; Gene Expression Regulation ; Genes ; Genetics ; Histone-Lysine N-Methyltransferase ; Histones ; Histones - metabolism ; Humans ; Intracellular Signaling Peptides and Proteins - metabolism ; Intracellular Signaling Peptides and Proteins - physiology ; Lysine - metabolism ; Mammary glands ; Mammary Glands, Animal - cytology ; Mammary Glands, Animal - growth & development ; Mammary Glands, Animal - metabolism ; Mesenchymal stem cells ; Methylation ; Mice ; Multipotent stem cells ; Phenotype ; Progenitor cells ; Rodents ; Small interfering RNA ; Stem cells ; Stem Cells - metabolism ; Wnt Proteins - genetics ; Wnt Proteins - metabolism</subject><ispartof>The Journal of cell biology, 2009-06, Vol.185 (5), p.811-826</ispartof><rights>Copyright Rockefeller University Press Jun 1, 2009</rights><rights>2009 Gu et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-cdaa2ce66b1028c1dda6afb31265ce9251151cfe1c728dca2cbc8f644d42e3eb3</citedby><cites>FETCH-LOGICAL-c500t-cdaa2ce66b1028c1dda6afb31265ce9251151cfe1c728dca2cbc8f644d42e3eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19487454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gu, Bingnan</creatorcontrib><creatorcontrib>Sun, Peng</creatorcontrib><creatorcontrib>Yuan, Yuanyang</creatorcontrib><creatorcontrib>Moraes, Ricardo C.</creatorcontrib><creatorcontrib>Li, Aihua</creatorcontrib><creatorcontrib>Teng, Andy</creatorcontrib><creatorcontrib>Agrawal, Anshu</creatorcontrib><creatorcontrib>Rhéaume, Catherine</creatorcontrib><creatorcontrib>Bilanchone, Virginia</creatorcontrib><creatorcontrib>Veltmaat, Jacqueline M.</creatorcontrib><creatorcontrib>Takemaru, Ken-Ichi</creatorcontrib><creatorcontrib>Millar, Sarah</creatorcontrib><creatorcontrib>Lee, Eva Y.-H. P.</creatorcontrib><creatorcontrib>Lewis, Michael T.</creatorcontrib><creatorcontrib>Li, Boan</creatorcontrib><creatorcontrib>Dai, Xing</creatorcontrib><title>Pygo2 Expands Mammary Progenitor Cells by Facilitating Histone H3 K4 Methylation</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>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.</description><subject>Animals</subject><subject>beta Catenin - genetics</subject><subject>beta Catenin - metabolism</subject><subject>Breasts</subject><subject>Cell Cycle</subject><subject>Cell Proliferation</subject><subject>Cells</subject><subject>Chromatin</subject><subject>Epithelial cells</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetics</subject><subject>Histone-Lysine N-Methyltransferase</subject><subject>Histones</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Intracellular Signaling Peptides and Proteins - physiology</subject><subject>Lysine - metabolism</subject><subject>Mammary glands</subject><subject>Mammary Glands, Animal - cytology</subject><subject>Mammary Glands, Animal - growth & development</subject><subject>Mammary Glands, Animal - metabolism</subject><subject>Mesenchymal stem cells</subject><subject>Methylation</subject><subject>Mice</subject><subject>Multipotent stem cells</subject><subject>Phenotype</subject><subject>Progenitor cells</subject><subject>Rodents</subject><subject>Small interfering RNA</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Wnt Proteins - genetics</subject><subject>Wnt Proteins - metabolism</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtPGzEUhS3UCgLtkmUrqwt2Q-_1Yx6bSigCggpqFu3a8ng8wdHETu1J1fz7OkoUCisvzqdP9_gQcolwjVDzr0vTXjOAGgE5PyETlAKKGgW8IxMAhkUjmTwj5yktAUBUgp-SM2xEXQkpJmQ-3y4Co7d_19p3iT7p1UrHLZ3HsLDejSHSqR2GRNstvdPGDW7Uo_MLOnNpDN7SGaffBX2y4_N2yEnwH8j7Xg_Jfjy8F-TX3e3P6ax4_HH_ML15LIwEGAvTac2MLcsWgdUGu06Xum85slIa2zCJKNH0Fk3F6s5ktjV1XwrRCWa5bfkF-bb3rjftynbG-jHqQa2j2xVQQTv1OvHuWS3CH8WqrG54FlwdBDH83tg0qpVLJpfV3oZNUmXFoW6aJoNf3oDLsIk-l1MMK2SyYTtbsYdMDClF2x8vQVC7oVQeSh2Hyvzn_89_oQ_LZODTHljmj47HnIHkFc-Gf0EqmNM</recordid><startdate>20090601</startdate><enddate>20090601</enddate><creator>Gu, Bingnan</creator><creator>Sun, Peng</creator><creator>Yuan, Yuanyang</creator><creator>Moraes, Ricardo C.</creator><creator>Li, Aihua</creator><creator>Teng, Andy</creator><creator>Agrawal, Anshu</creator><creator>Rhéaume, Catherine</creator><creator>Bilanchone, Virginia</creator><creator>Veltmaat, Jacqueline M.</creator><creator>Takemaru, Ken-Ichi</creator><creator>Millar, Sarah</creator><creator>Lee, Eva Y.-H. 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P.</creatorcontrib><creatorcontrib>Lewis, Michael T.</creatorcontrib><creatorcontrib>Li, Boan</creatorcontrib><creatorcontrib>Dai, Xing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gu, Bingnan</au><au>Sun, Peng</au><au>Yuan, Yuanyang</au><au>Moraes, Ricardo C.</au><au>Li, Aihua</au><au>Teng, Andy</au><au>Agrawal, Anshu</au><au>Rhéaume, Catherine</au><au>Bilanchone, Virginia</au><au>Veltmaat, Jacqueline M.</au><au>Takemaru, Ken-Ichi</au><au>Millar, Sarah</au><au>Lee, Eva Y.-H. P.</au><au>Lewis, Michael T.</au><au>Li, Boan</au><au>Dai, Xing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pygo2 Expands Mammary Progenitor Cells by Facilitating Histone H3 K4 Methylation</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2009-06-01</date><risdate>2009</risdate><volume>185</volume><issue>5</issue><spage>811</spage><epage>826</epage><pages>811-826</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>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.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>19487454</pmid><doi>10.1083/jcb.200810133</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals beta Catenin - genetics beta Catenin - metabolism Breasts Cell Cycle Cell Proliferation Cells Chromatin Epithelial cells Gene Expression Regulation Genes Genetics Histone-Lysine N-Methyltransferase Histones Histones - metabolism Humans Intracellular Signaling Peptides and Proteins - metabolism Intracellular Signaling Peptides and Proteins - physiology Lysine - metabolism Mammary glands Mammary Glands, Animal - cytology Mammary Glands, Animal - growth & development Mammary Glands, Animal - metabolism Mesenchymal stem cells Methylation Mice Multipotent stem cells Phenotype Progenitor cells Rodents Small interfering RNA Stem cells Stem Cells - metabolism Wnt Proteins - genetics Wnt Proteins - metabolism |
| title | Pygo2 Expands Mammary Progenitor Cells by Facilitating Histone H3 K4 Methylation |
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