Open AccessA regulative epigenetic circuit supervised by HDAC7 represses IGFBP6 and IGFBP7 expression to sustain mammary stemness
Author(s) -
Eros Di Giorgio,
Valentina Cutano,
Martina Minisini,
Vanessa Tolotto,
Emiliano Dalla,
Claudio Brancolini
Publication year - 2021
Publication title -
epigenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.265
H-Index - 60
eISSN - 1750-1911
pISSN - 1750-192X
DOI - 10.2217/epi-2020-0347
Subject(s) - mef2 , retinoic acid , gene silencing , epigenetics , psychological repression , biology , downregulation and upregulation , signal transduction , cancer research , transcription factor , microbiology and biotechnology , gene expression , genetics , gene , enhancer
Background: In the breast, the pleiotropic epigenetic regulator HDAC7 can influence stemness. Materials & Methods: The authors used MCF10 cells knocked-out for HDAC7 to explore the contribution of HDAC7 to IGF1 signaling. Results: HDAC7 buffers H3K27ac levels at the IGFBP6 and IGFBP7 genomic loci and influences their expression. In this manner, HDAC7 can tune IGF1 signaling to sustain stemness. In HDAC7 knocked-out cells, RXRA promotes the upregulation of IGFBP6/7 mRNAs. By contrast, HDAC7 increases FABP5 expression, possibly through repression of miR-218. High levels of FABP5 can reduce the delivery of all-trans-retinoic acid to RXRA. Accordingly, the silencing of FABP5 increases IGFBP6 and IGFBP7 expression and reduces mammosphere generation. Conclusion: The authors propose that HDAC7 controls the uptake of all-trans-retinoic acid, thus influencing RXRA activity and IGF1 signaling.