Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation
Copyright policy )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 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/β-catenin signaling on progenitor cell regulation and cell cycle gene expression, and loss of epithelial Pygo2 completely rescues β-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/β-catenin target loci, via direct binding to K4-methyl histone H3 and recruiting histone H3 K4 methyltransferase complexes.
- Baylor College of Medicine United States
- Stony Brook University United States
- UNIVERSITY OF CALIFORNIA IRVINE
- Agency for Science, Technology and Research Singapore
- State University of New York at Potsdam United States
Gene Expression Regulation (mesh), PHD-FINGER, Women's Health (rcdc), Wnt Proteins (mesh), Regenerative Medicine, 11 Medical and Health Sciences (for), Medical and Health Sciences, 3105 Genetics (for-2020), BETA-CATENIN, Histones, Regenerative Medicine (rcdc), Mice, Stem Cell Research - Nonembryonic - Human, 31 Biological sciences (for-2020), 2.1 Biological and endogenous factors, Animals (mesh), Cell Proliferation (mesh), 32 Biomedical and Clinical Sciences (for-2020), Stem Cell Research - Nonembryonic - Human (rcdc), Cell Cycle (mesh), Research Articles, beta Catenin, GENE-EXPRESSION, Lysine (mesh), Stem Cells (mesh), Developmental Biology (science-metrix), Humans (mesh), Stem Cells, Cell Cycle, Intracellular Signaling Peptides and Proteins, Mice (mesh), Biological Sciences, Histone Methyltransferases (mesh), Histones (mesh), Mammary Glands, Phenotype (mesh), 06 Biological Sciences (for), Phenotype, Histone Methyltransferases, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Non-Human (rcdc), Histone-Lysine N-Methyltransferase (mesh), beta Catenin (mesh), 1.1 Normal biological development and functioning, Intracellular Signaling Peptides and Proteins (mesh), 610, Methylation, NUCLEAR-PROTEIN, Mammary Glands, Animal, GLAND DEVELOPMENT, P21 LOSS, Genetics, BREAST-CANCER, Animals, Humans, WNT SIGNALING PATHWAY, Animal (mesh), Cell Proliferation, 1.1 Normal biological development and functioning (hrcs-rac), 31 Biological Sciences (for-2020), Biomedical and Clinical Sciences, Animal, Genetics (rcdc), Lysine, 2.1 Biological and endogenous factors (hrcs-rac), Methylation (mesh), Histone-Lysine N-Methyltransferase, Stem Cell Research, Stem Cell Research (rcdc), STEM-CELL, 3101 Biochemistry and Cell Biology (for-2020), Wnt Proteins, DNA-DAMAGE, 32 Biomedical and clinical sciences (for-2020), Gene Expression Regulation, Women's Health, Biochemistry and Cell Biology, Developmental Biology
Gene Expression Regulation (mesh), PHD-FINGER, Women's Health (rcdc), Wnt Proteins (mesh), Regenerative Medicine, 11 Medical and Health Sciences (for), Medical and Health Sciences, 3105 Genetics (for-2020), BETA-CATENIN, Histones, Regenerative Medicine (rcdc), Mice, Stem Cell Research - Nonembryonic - Human, 31 Biological sciences (for-2020), 2.1 Biological and endogenous factors, Animals (mesh), Cell Proliferation (mesh), 32 Biomedical and Clinical Sciences (for-2020), Stem Cell Research - Nonembryonic - Human (rcdc), Cell Cycle (mesh), Research Articles, beta Catenin, GENE-EXPRESSION, Lysine (mesh), Stem Cells (mesh), Developmental Biology (science-metrix), Humans (mesh), Stem Cells, Cell Cycle, Intracellular Signaling Peptides and Proteins, Mice (mesh), Biological Sciences, Histone Methyltransferases (mesh), Histones (mesh), Mammary Glands, Phenotype (mesh), 06 Biological Sciences (for), Phenotype, Histone Methyltransferases, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Non-Human (rcdc), Histone-Lysine N-Methyltransferase (mesh), beta Catenin (mesh), 1.1 Normal biological development and functioning, Intracellular Signaling Peptides and Proteins (mesh), 610, Methylation, NUCLEAR-PROTEIN, Mammary Glands, Animal, GLAND DEVELOPMENT, P21 LOSS, Genetics, BREAST-CANCER, Animals, Humans, WNT SIGNALING PATHWAY, Animal (mesh), Cell Proliferation, 1.1 Normal biological development and functioning (hrcs-rac), 31 Biological Sciences (for-2020), Biomedical and Clinical Sciences, Animal, Genetics (rcdc), Lysine, 2.1 Biological and endogenous factors (hrcs-rac), Methylation (mesh), Histone-Lysine N-Methyltransferase, Stem Cell Research, Stem Cell Research (rcdc), STEM-CELL, 3101 Biochemistry and Cell Biology (for-2020), Wnt Proteins, DNA-DAMAGE, 32 Biomedical and clinical sciences (for-2020), Gene Expression Regulation, Women's Health, Biochemistry and Cell Biology, Developmental Biology
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