Format

Send to

Choose Destination
Cell. 2007 Feb 9;128(3):505-518. doi: 10.1016/j.cell.2006.12.038.

Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors.

Author information

1
Howard Hughes Medical Institute, Department of Molecular Medicine, University of California, San Diego, School of Medicine 9500 Gilman Drive, La Jolla, CA 92093-0648.
2
Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine 9500 Gilman Drive, La Jolla, CA 92093-0648.
3
Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, School of Medicine 9500 Gilman Drive, La Jolla, CA 92093-0648.
#
Contributed equally

Abstract

Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.

PMID:
17289570
PMCID:
PMC1994663
DOI:
10.1016/j.cell.2006.12.038
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center