Inhibitor of differentiation 4 (ID4) represses mammary myoepithelial differentiation via inhibition of HEB
Details
Publication Year 2021-02-19,Volume 24,Issue #2,Page 102072
Journal Title
iScience
Abstract
Inhibitor of differentiation (ID) proteins dimerize with basic HLH (bHLH) transcription factors, repressing transcription of lineage-specification genes across diverse cellular lineages. ID4 is a key regulator of mammary stem cells; however, the mechanism by which it achieves this is unclear. Here, we show that ID4 has a cell autonomous role in preventing myoepithelial differentiation of basal cells in mammary organoids and in vivo. ID4 positively regulates proliferative genes and negatively regulates genes involved in myoepithelial function. Mass spectrometry reveals that ID4 interacts with the bHLH protein HEB, which binds to E-box motifs in regulatory elements of basal developmental genes involved in extracellular matrix and the contractile cytoskeleton. We conclude that high ID4 expression in mammary basal stem cells antagonizes HEB transcriptional activity, preventing myoepithelial differentiation and allowing for appropriate tissue morphogenesis. Downregulation of ID4 during pregnancy modulates gene regulated by HEB, promoting specialization of basal cells into myoepithelial cells.
Publisher
Elsevier
Keywords
cell biology; developmental biology; molecular biology; stem cells research;
Research Division(s)
Cancer Biology And Stem Cells
PubMed ID
33554073
Open Access at Publisher's Site
https://doi.org/10.1016/j.isci.2021
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-03-09 01:36:48
Last Modified: 2021-03-09 02:09:30
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