Long noncoding RNA as modular scaffold of histone modification complexes

Science. 2010 Aug 6;329(5992):689-93. doi: 10.1126/science.1192002. Epub 2010 Jul 8.

Abstract

Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Carrier Proteins / metabolism
  • Cell Line
  • Cells, Cultured
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Co-Repressor Proteins
  • DNA-Binding Proteins / metabolism*
  • Enhancer of Zeste Homolog 2 Protein
  • HeLa Cells
  • Histone Demethylases / metabolism*
  • Histones / metabolism*
  • Humans
  • Methylation
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / metabolism*
  • Repressor Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Chromatin
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Histones
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Polycomb-Group Proteins
  • RCOR1 protein, human
  • RE1-silencing transcription factor
  • RNA, Untranslated
  • Repressor Proteins
  • SUZ12 protein, human
  • Transcription Factors
  • Histone Demethylases
  • KDM1A protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE22345