Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts
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Young_Let-7 represses.pdf
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Author(s)
Gurtan, Allan M.
Ravi, Arvind
Bosson, Andrew David
JnBaptiste, Courtney Kenneil
Bhutkar, Arjun (AJ)
Whittaker, Charles A.
Young, Richard A.
Sharp, Phillip A.
Rahl, Peter B.
Date Issued
April 2013
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Gurtan, A. M., A. Ravi, P. B. Rahl, A. D. Bosson, C. K. JnBaptiste, A. Bhutkar, C. A. Whittaker, R. A. Young, and P. A. Sharp. “Let-7 Represses Nr6a1 and a Mid-Gestation Developmental Program in Adult Fibroblasts.” Genes & Development 27, no. 8 (April 15, 2013): 941–954. Copyright © 2013 by Cold Spring Harbor Laboratory Press
Version
Final published version
Abstract
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function.
MIT Department
Whitaker College of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution‐NonCommercial License
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DOI of Published Version
https://doi.org/10.1101/gad.215376.113
