Journal article
Three-dimensional genome architecture coordinates key regulators of lineage specification in mammary epithelial cells
MJG Milevskiy, HD Coughlan, SR Kane, TM Johanson, S Kordafshari, WF Chan, M Tsai, E Surgenor, S Wilcox, RS Allan, Y Chen, GJ Lindeman, GK Smyth, JE Visvader
Cell Genomics | Published : 2023
Abstract
Although lineage-specific genes have been identified in the mammary gland, little is known about the contribution of the 3D genome organization to gene regulation in the epithelium. Here, we describe the chromatin landscape of the three major epithelial subsets through integration of long- and short-range chromatin interactions, accessibility, histone modifications, and gene expression. While basal genes display exquisite lineage specificity via distal enhancers, luminal-specific genes show widespread promoter priming in basal cells. Cell specificity in luminal progenitors is largely mediated through extensive chromatin interactions with super-enhancers in gene-body regions in addition to in..
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Grants
Awarded by Breast Cancer Research Foundation
Funding Acknowledgements
We are grateful to B. Pal, H. Huckstep, and L. Prokopuk for expert advice and to the WEHI Bioservices, FACS, Research Computing, and Genomics facilities. This work was supported by the NBCF (IIRS-20-022) , NHMRC (1054618, 1100807, 1113133, 1153049) , NHMRC IRIISS, Victorian State Government Operational Infrastructure Support, and BCRF (USA) . M.J.G.M. was supported by a VCA fellowship (ECRF19011) , H.D.C. was supported by the Marian and E.H. Flack Fellowship, Y.C. was supported by an MRFF Investigator grant (1176199) , and G.J.L., G.K.S., and J.E.V. were supported by NHMRC fellowships (G.J.L. 1078730, 1175960; G.K.S. 1058892; J.E.V. 1037230, 1102742) .