Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2
The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked diffe...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713000077 |
| _version_ | 1818788890436173824 |
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| author | Bhupinder Pal Toula Bouras Wei Shi François Vaillant Julie M. Sheridan Naiyang Fu Kelsey Breslin Kun Jiang Matthew E. Ritchie Matthew Young Geoffrey J. Lindeman Gordon K. Smyth Jane E. Visvader |
| author_facet | Bhupinder Pal Toula Bouras Wei Shi François Vaillant Julie M. Sheridan Naiyang Fu Kelsey Breslin Kun Jiang Matthew E. Ritchie Matthew Young Geoffrey J. Lindeman Gordon K. Smyth Jane E. Visvader |
| author_sort | Bhupinder Pal |
| collection | DOAJ |
| description | The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked differences in H3K27 trimethylation between subpopulations in the adult gland suggest that epithelial cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, the mammary epigenome underwent highly specific changes in different hormonal contexts, with a profound change being observed in the global H3K27me3 map of luminal cells during pregnancy. We therefore examined the role of the key H3K27 methyltransferase Ezh2 in mammary physiology. Its expression and phosphorylation coincided with H3K27me3 modifications and peaked during pregnancy, driven in part by progesterone. Targeted deletion of Ezh2 impaired alveologenesis during pregnancy, preventing lactation, and drastically reduced stem/progenitor cell numbers. Taken together, these findings reveal that Ezh2 couples hormonal stimuli to epigenetic changes that underpin progenitor activity, lineage specificity, and alveolar expansion in the mammary gland. |
| first_indexed | 2024-12-18T14:30:51Z |
| format | Article |
| id | doaj.art-a9d58ea584384454b49ee4fbf86fdd9a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-18T14:30:51Z |
| publishDate | 2013-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a9d58ea584384454b49ee4fbf86fdd9a2022-12-21T21:04:35ZengElsevierCell Reports2211-12472013-02-013241142610.1016/j.celrep.2012.12.020Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2Bhupinder Pal0Toula Bouras1Wei Shi2François Vaillant3Julie M. Sheridan4Naiyang Fu5Kelsey Breslin6Kun Jiang7Matthew E. Ritchie8Matthew Young9Geoffrey J. Lindeman10Gordon K. Smyth11Jane E. Visvader12ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked differences in H3K27 trimethylation between subpopulations in the adult gland suggest that epithelial cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, the mammary epigenome underwent highly specific changes in different hormonal contexts, with a profound change being observed in the global H3K27me3 map of luminal cells during pregnancy. We therefore examined the role of the key H3K27 methyltransferase Ezh2 in mammary physiology. Its expression and phosphorylation coincided with H3K27me3 modifications and peaked during pregnancy, driven in part by progesterone. Targeted deletion of Ezh2 impaired alveologenesis during pregnancy, preventing lactation, and drastically reduced stem/progenitor cell numbers. Taken together, these findings reveal that Ezh2 couples hormonal stimuli to epigenetic changes that underpin progenitor activity, lineage specificity, and alveolar expansion in the mammary gland.http://www.sciencedirect.com/science/article/pii/S2211124713000077 |
| spellingShingle | Bhupinder Pal Toula Bouras Wei Shi François Vaillant Julie M. Sheridan Naiyang Fu Kelsey Breslin Kun Jiang Matthew E. Ritchie Matthew Young Geoffrey J. Lindeman Gordon K. Smyth Jane E. Visvader Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2 Cell Reports |
| title | Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2 |
| title_full | Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2 |
| title_fullStr | Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2 |
| title_full_unstemmed | Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2 |
| title_short | Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2 |
| title_sort | global changes in the mammary epigenome are induced by hormonal cues and coordinated by ezh2 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713000077 |
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