Journal
DEVELOPMENTAL CELL
Volume 53, Issue 5, Pages 561-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2020.05.007
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Funding
- NIH NIAMS Arthritis and Musculoskeletal and Skin Diseases [AR47364, AR60306]
- Institute of General Medical Sciences [GM125322]
- China Medical University and Hospital in Taiwan (CMU) (USC grant) [5351285884]
- Postdoctoral Research Abroad Program, Ministry of Science and Technology (MOST), Taiwan [102-2917-I-564002-A1, 107-2917-I-564-024]
- NIH T90 [5T90DE021982]
- USC Craniofacial Biology Ph.D. Program, Study Abroad Scholarship MOST [1040120022]
- Cell and Tissue Imaging Core of the USC Research Center for Liver Diseases, NIH [P30 DK048522]
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Regional specification is critical for skin development, regeneration, and evolution. The contribution of epigenetics in this process remains unknown. Here, using avian epidermis, we find two major strategies regulate beta-keratin gene clusters. (1) Over the body, macro-regional specificities (scales, feathers, claws, etc.) established by typical enhancers control five subclusters located within the epidermal differentiation complex on chromosome 25; (2) within a feather, micro-regional specificities are orchestrated by temporospatial chromatin looping of the feather beta-keratin gene cluster on chromosome 27. Analyses suggest a three-factor model for regional specification: competence factors (e.g., AP1) make chromatin accessible, regional specifiers (e.g., Zic1) target specific genome regions, and chromatin regulators (e.g., CTCF and SATBs) establish looping configurations. Gene perturbations disrupt morphogenesis and histo-differentiation. This chicken skin paradigm advances our understanding of how regulation of big gene clusters can set up a two-dimensional body surface map.
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