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RESEARCH COMMUNICATION

Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3

VA Palo Alto Health Care System, Palo Alto, California 94305, USA; Programs in Epithelial Biology and Cancer Biology and the Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA

The recent discovery of H3K27me3 demethylases suggests that H3K27me3 may dynamically regulate gene expression, but this potential role in mammalian tissue homeostasis remains uncharacterized. In the epidermis, a tissue that balances stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of many differentiation genes. During calcium-induced differentiation, H3K27me3 was erased at these promoters in concert with loss of PcG protein occupancy and increased binding by the H3K27me3 demethylase, JMJD3. Within epidermal tissue, JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced it. These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation.

[Keywords: Chromatin; differentiation; stem cell; epigenetics; gene regulation; histones]

Received March 12, 2008; revised version accepted May 22, 2008.

E-MAIL Khavari{at}stanford.edu; FAX (650) 723-8762.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1673508.

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