A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation
Open accessAbstract
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.
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The human epidermis is a constantly renewing stratified epithelial tissue, and thousands of genes change in expression during terminal epidermal differentiation as progenitor cells migrate from the basal layer, begin keratinization, and undergo cornification.
“The human epidermis is a constantly renewing stratified epithelial tissue, and thousands of genes change in expression during terminal epidermal differentiation as progenitor cells migrate from the basal layer, begin keratinization, and undergo cornification to form the outer layer of the skin. (Lopez-Pajares et al., 2015).”
From Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks (2019) · cites this paper as Lopez-Pajares et al., 2015
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References 70 · Cited by 194
- Authors
- Lopez-Pajares, V., Qu, K., Zhang, J., Webster, D. E., Barajas, B. C., Siprashvili, Z., Zarnegar, B. J., Boxer, L. D., Rios, E. J., Tao, S., Kretz, M., & Khavari, P. A.
- Affiliations
- Stanford University (US)
- University of Regensburg (DE)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Khavari, Paul A.
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 32
- Issue
- 6
- Pages
- 693-706
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC4456036
- OpenAlex
- W2108862219
- Cited by
- 194
- References
- 70
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 13 · 2023: 20 · 2022: 17 · 2021: 13 · 2020: 29 · 2019: 18 · 2018: 21 · 2017: 19 · 2016: 19 · 2015: 9
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- National Institutes of Health (1f32ca142002-01a1)
- National Cancer Institute (F32CA142090, F32 CA1420902, F32 CA142002, T32CA009302)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR45192, R01AR045192, AR 45192)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- epidermal differentiation, MAF, MAFB, TINCR, transcriptional regulatory networks, epidermal regeneration, progenitor cell differentiation, GRHL3, ZNF750, KLF4, Blimp-1
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Epidermal Cells, Kruppel-Like Factor 4, Animals, Cell Differentiation, DNA-Binding Proteins, Female, Humans, Repressor Proteins, Transcription Factors, Mice, SCID, Mice, Inbred NOD, Gene Transfer Techniques, Gene Expression Regulation, Developmental, Gene Expression Profiling, Tumor Suppressor Proteins, RNA Interference, RNA, Small Interfering, Organogenesis, Proto-Oncogene Proteins c-maf, MafB Transcription Factor, Mice, Kruppel-Like Transcription Factors, RNA, Long Noncoding
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