Apr 10, 2020

ID4 represses myoepithelial differentiation of mammary stem cells through its interaction with HEB

BioRxiv : the Preprint Server for Biology
H. HollidayAlexander Swarbrick

Abstract

Differentiation of stem cells embedded within the mammary epithelium is orchestrated by lineage-specifying transcription factors. Unlike the well-defined luminal hierarchy, dissection of the basal lineage has been hindered by a lack of specific markers. Inhibitor of Differentiation 4 (ID4) is a basally-restricted helix-loop-helix (HLH) transcription factor essential for mammary development. Here we show that ID4 is highly expressed in basal stem cells and decreases during myoepithelial differentiation. By integrating transcriptomic, proteomic, and ChIP-sequencing data, we reveal that ID4 is required to suppress myoepithelial gene expression and cell fate. We identify the bHLH protein HEB as a direct binding partner of ID4, and describe a previously-unknown role for this regulator in mammary development. HEB binds to E-boxes in regulatory elements of developmental genes, negatively regulated by ID4, involved in extracellular matrix synthesis and contraction. Together our findings support a model whereby HEB promotes myoepithelial specialisation by cis-transcriptional regulation, which is opposed by biochemical interaction with ID4. These new insights expand our current understanding into control of myoepithelial differentiation ...Continue Reading

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Mentioned in this Paper

Research
Genome
Corn extract
Nucleic Acid Sequencing
Zea mays
Zea mays antigen
Site
Biologic Preservation
Sequencing
Species

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