title: A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation.
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.
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Vanessa
authors: V
authors: Lopez-Pajares
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Kun
authors: K
authors: Qu
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Jiajing
authors: J
authors: Zhang
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Dan E
authors: DE
authors: Webster
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Brook C
authors: BC
authors: Barajas
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Zurab
authors: Z
authors: Siprashvili
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Brian J
authors: BJ
authors: Zarnegar
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Lisa D
authors: LD
authors: Boxer
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Eon J
authors: EJ
authors: Rios
authors: Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
authors: Shiying
authors: S
authors: Tao
authors: Institute of Biochemistry, Genetics and Microbiology, University of Regensburg, 93053 Regensburg, Germany.
authors: Markus
authors: M
authors: Kretz
authors: 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.
authors: Paul A
authors: PA
authors: Khavari
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D000078404:Epidermal Cells; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis; D051258:MafB Transcription Factor / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D038081:Organogenesis / Q000235:genetics; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; C473143:GRHL3 protein, human; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C495607:MAF protein, human; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D051257:Proto-Oncogene Proteins c-maf; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C570799:ZNF750 protein, human; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1