Lineage Specific Methylation of the Elf5 Promoter in Mammary Epithelial Cells
Author(s) -
Lee Heather J.,
Hinshelwood Rebecca A.,
Bouras Toula,
GallegoOrtega David,
ValdésMora Fátima,
Blazek Katrina,
Visvader Jane E.,
Clark Susan J.,
Ormandy Christopher J.
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.706
Subject(s) - biology , methylation , lineage (genetic) , dna methylation , cell lineage , stem cell , gene , microbiology and biotechnology , genetics , cancer research , cellular differentiation , gene expression
Abstract 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. S TEM C ELLS 2011;29:1611–1619