Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 28, Pages 11667-11672Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0904715106
Keywords
histone modifications; epigenetic regulation; polycomb
Categories
Funding
- National Institutes of Health [HL007893]
- National Human Genome Research Institute
- Broad Institute of MIT and Harvard.
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We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc) RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, weexpand the catalog of human lincRNAs to approximate to 3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC) 2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that approximate to 20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression.
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