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Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte Differentiation

Authors: Chun-Yuan Chen; Rainer B. Lanz; Christopher J. Walkey; Wen-Hsuan Chang; Wange Lu; Deborah L. Johnson;

Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte Differentiation

Abstract

RNA polymerase (pol) III transcribes a variety of small untranslated RNAs involved in transcription, RNA processing, and translation. RNA pol III and its components are altered in various human developmental disorders, yet their roles in cell fate determination and development are poorly understood. Here we demonstrate that Maf1, a transcriptional repressor, promotes induction of mouse embryonic stem cells (mESCs) into mesoderm. Reduced Maf1 expression in mESCs and preadipocytes impairs adipogenesis, while ectopic Maf1 expression in Maf1-deficient cells enhances differentiation. RNA pol III repression by chemical inhibition or knockdown of Brf1 promotes adipogenesis. Altered RNA pol III-dependent transcription produces select changes in mRNAs with a significant enrichment of adipogenic gene signatures. Furthermore, RNA pol III-mediated transcription positively regulates long non-coding RNA H19 and Wnt6 expression, established adipogenesis inhibitors. Together, these studies reveal an important and unexpected function for RNA pol III-mediated transcription and Maf1 in mesoderm induction and adipocyte differentiation.

Keywords

Male, QH301-705.5, Primary Cell Culture, Mice, Nude, Article, Mesoderm, Mice, Proto-Oncogene Proteins, Adipocytes, Animals, Biology (General), RNA, Small Interfering, Embryoid Bodies, Adipogenesis, Gene Expression Regulation, Developmental, Nuclear Proteins, RNA Polymerase III, RNA-Binding Proteins, Cell Differentiation, Mouse Embryonic Stem Cells, Fibroblasts, RNA, Long Noncoding, Butyrate Response Factor 1

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    popularity
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
26
Top 10%
Average
Top 10%
Green
gold