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Original Research: Tissue-Specific Stem Cells
Version of Record online: 27 SEP 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 10, pages 1611–1619, October 2011
How to Cite
Lee, H. J., Hinshelwood, R. A., Bouras, T., Gallego-Ortega, D., Valdés-Mora, F., Blazek, K., Visvader, J. E., Clark, S. J. and Ormandy, C. J. (2011), Lineage Specific Methylation of the Elf5 Promoter in Mammary Epithelial Cells. STEM CELLS, 29: 1611–1619. doi: 10.1002/stem.706
Author contributions: H.J.L., R.A.H., D.G.-O., and F.V.-M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; T.B.: provision of study materials or patients, final approval of manuscript; K.B.: collection and/or assembly of data, final approval of manuscript; J.E.V.: financial support, provision of study materials or patients, final approval of manuscript; S.J.C. and C.J.O.: conception and design, financial support, data analysis and interpretation, final approval of manuscript. H.J.L. and R.A.H contributed equally to this article. S.J.C. and C.J.O. are joint senior authors of this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS August 5, 2011.
- Issue online: 27 SEP 2011
- Version of Record online: 27 SEP 2011
- Accepted manuscript online: 5 AUG 2011 08:00AM EST
- Manuscript Accepted: 18 JUL 2011
- Manuscript Received: 15 DEC 2010
- National Health & Medical Research Council of Australia
- Australian Cancer Research Foundation
- National Breast Cancer Foundation
- RT Hall Trust
Recent characterization of mammary stem and progenitor cells has improved our understanding of the transcriptional network that coordinates mammary development; however, little is known about the mechanisms that enforce lineage commitment and prevent transdifferentiation in the mammary gland. The E-twenty six transcription factor Elf5 forces the differentiation of mammary luminal progenitor cells to establish the milk producing alveolar lineage. Methylation of the Elf5 promoter has been proposed to act as a lineage gatekeeper during embryonic development. We used bisulphite sequencing to investigate in detail whether Elf5 promoter methylation plays a role in lineage commitment during mammary development. An increase in Elf5 expression was associated with decreasing Elf5 promoter methylation in differentiating HC11 mammary cells. Similarly, purified mammary epithelial cells from mice had increased Elf5 expression and decreased promoter methylation during pregnancy. Finally, analysis of epithelial subpopulations revealed that the Elf5 promoter is methylated and silenced in the basal, stem cell-containing population relative to luminal cells. These results demonstrate that Elf5 promoter methylation is lineage-specific and developmentally regulated in the mammary gland in vivo, and suggest that loss of Elf5 methylation specifies the mammary luminal lineage, while continued Elf5 methylation maintains the stem cell and myoepithelial lineages. STEM CELLS 2011;29:1611–1619