Lineage specific methylation of the Elf5 promoter in mammary epithelial cells.

Lee, HJ; Hinshelwood, RA; Bouras, T; Gallego-Ortega, D; Valdés-Mora, F; Blazek, K; Visvader, JE; Clark, SJ; Ormandy, CJ

Lineage specific methylation of the Elf5 promoter in mammary epithelial cells.

Lee, HJ Hinshelwood, RA Bouras, T Gallego-Ortega, D Valdés-Mora, F Blazek, K Visvader, JE Clark, SJ Ormandy, CJ

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Publisher:: WILEY-BLACKWELL
Publication Type:: Journal Article
Citation:: Stem Cells, 2011, 29, (10), pp. 1611-1619
Issue Date:: 2011-10

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Field	Value	Language
dc.contributor.author	Lee, HJ
dc.contributor.author	Hinshelwood, RA
dc.contributor.author	Bouras, T
dc.contributor.author	Gallego-Ortega, D
dc.contributor.author	Valdés-Mora, F
dc.contributor.author	Blazek, K
dc.contributor.author	Visvader, JE
dc.contributor.author	Clark, SJ
dc.contributor.author	Ormandy, CJ
dc.date.accessioned	2023-02-27T19:35:28Z
dc.date.available	2023-02-27T19:35:28Z
dc.date.issued	2011-10
dc.identifier.citation	Stem Cells, 2011, 29, (10), pp. 1611-1619
dc.identifier.issn	1066-5099
dc.identifier.issn	1549-4918
dc.identifier.uri	http://hdl.handle.net/10453/166473
dc.description.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.
dc.format	Print
dc.language	eng
dc.publisher	WILEY-BLACKWELL
dc.relation.ispartof	Stem Cells
dc.relation.isbasedon	10.1002/stem.706
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	06 Biological Sciences, 10 Technology, 11 Medical and Health Sciences
dc.subject.classification	Immunology
dc.subject.mesh	Animals
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Cell Lineage
dc.subject.mesh	DNA Methylation
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression Regulation, Developmental
dc.subject.mesh	Male
dc.subject.mesh	Mammary Glands, Animal
dc.subject.mesh	Mice
dc.subject.mesh	Pregnancy
dc.subject.mesh	Promoter Regions, Genetic
dc.subject.mesh	RNA, Small Interfering
dc.subject.mesh	Sequence Analysis, DNA
dc.subject.mesh	Stem Cells
dc.subject.mesh	Transcription Factors
dc.subject.mesh	Transfection
dc.subject.mesh	Mammary Glands, Animal
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Stem Cells
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Transcription Factors
dc.subject.mesh	RNA, Small Interfering
dc.subject.mesh	Transfection
dc.subject.mesh	Sequence Analysis, DNA
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	DNA Methylation
dc.subject.mesh	Gene Expression Regulation, Developmental
dc.subject.mesh	Cell Lineage
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Promoter Regions, Genetic
dc.title	Lineage specific methylation of the Elf5 promoter in mammary epithelial cells.
dc.type	Journal Article
utslib.citation.volume	29
utslib.location.activity	England
utslib.for	06 Biological Sciences
utslib.for	10 Technology
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
dc.date.updated	2023-02-27T19:35:27Z
pubs.issue	10
pubs.publication-status	Published
pubs.volume	29
utslib.citation.issue	10

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.

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http://hdl.handle.net/10453/166473