Cell Reports
Volume 17, Issue 8, 15 November 2016, Pages 2060-2074
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Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks

https://doi.org/10.1016/j.celrep.2016.10.058Get rights and content
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Highlights

  • Epigenomes of four normal human breast cell fractions and three cell lines are reported

  • Luminal progenitor and mature luminal cell epigenomes differ greatly

  • Enhancers define luminal progenitors as intermediate between basal and luminal cells

  • Transcription factor binding sites in active enhancers point to distinct regulators

Summary

The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines. Each genome-wide analysis contains profiles for six histone marks, methylated DNA, and RNA transcripts. Analysis of these datasets shows that each cell type has unique features, primarily within genomic regulatory regions, and that the cell lines group together. Analyses of the promoter and enhancer profiles place the luminal progenitors in between the basal cells and the non-progenitor luminal subset. Integrative analysis reveals networks of subset-specific transcription factors.

Keywords

normal human breast
mammary cells
epigenomic
profiling
chromatin
enhancer
transcriptome
regulatory network
transcription factors
stem cells

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