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Dev Cell. 2015 Mar 23;32(6):693-706. doi: 10.1016/j.devcel.2015.01.028.

A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation.

Author information

1
Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
2
Institute of Biochemistry, Genetics and Microbiology, University of Regensburg, 93053 Regensburg, Germany.
3
Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94304, USA. Electronic address: khavari@stanford.edu.

Abstract

Progenitor differentiation requires remodeling of genomic expression; however, in many tissues, such as epidermis, the spectrum of remodeled genes and the transcription factors (TFs) that control them are not fully defined. We performed kinetic transcriptome analysis during regeneration of differentiated epidermis and identified gene sets enriched in progenitors (594 genes), in early (159 genes), and in late differentiation (387 genes). Module mapping of 1,046 TFs identified MAF and MAFB as necessary and sufficient for progenitor differentiation. MAF:MAFB regulated 393 genes altered in this setting. Integrative analysis identified ANCR and TINCR lncRNAs as essential upstream MAF:MAFB regulators. ChIP-seq analysis demonstrated MAF:MAFB binding to known epidermal differentiation TF genes whose expression they controlled, including GRHL3, ZNF750, KLF4, and PRDM1. Each of these TFs rescued expression of specific MAF:MAFB target gene subsets in the setting of MAF:MAFB loss, indicating they act downstream of MAF:MAFB. A lncRNA-TF network is thus essential for epidermal differentiation.

PMID:
25805135
PMCID:
PMC4456036
DOI:
10.1016/j.devcel.2015.01.028
[Indexed for MEDLINE]
Free PMC Article

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