PRC1 preserves epidermal tissue integrity independently of PRC2
- Idan Cohen1,
- Dejian Zhao2,10,11,
- Gopinathan Menon3,
- Manabu Nakayama4,
- Haruhiko Koseki5,6,
- Deyou Zheng7,8,9 and
- Elena Ezhkova1
- 1Black Family Stem Cell Institute, Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA;
- 2Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA;
- 3California Academy of Sciences, San Francisco, California 94118, USA;
- 4Department of Frontier Research and Development, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan;
- 5Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (RIKEN-IMS) Tsurumi-ku, Yokohama 230-0045, Japan;
- 6Advanced Research and Development Programs for Medical Innovation (AMED-CREST), Tsurumi-ku, Yokohama 230-0045, Japan;
- 7Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA;
- 8Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;
- 9Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA
- Corresponding author: elena.ezhkova{at}mssm.edu
Abstract
Polycomb-repressive complex 1 (PRC1) and PRC2 are critical chromatin regulators of gene expression and tissue development. Here, we show that despite extensive genomic cobinding, PRC1 is essential for epidermal integrity, whereas PRC2 is dispensable. Loss of PRC1 resulted in blistering skin, reminiscent of human skin fragility syndromes. Conversely, PRC1 does not restrict epidermal stratification during skin morphogenesis, whereas PRC2 does. Molecular dissection demonstrated that PRC1 functions with PRC2 to silence/dampen expression of adhesion genes. In contrast, PRC1 promotes expression of critical epidermal adhesion genes independently of PRC2-mediated H3K27me3. Together, we demonstrate a functional link between epigenetic regulation and skin diseases.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.319939.118.
- Received August 15, 2018.
- Accepted November 5, 2018.
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