LincRNA-1614 coordinates Sox2/PRC2-mediated repression of developmental genes in pluripotency maintenance

J Mol Cell Biol. 2018 Apr 1;10(2):118-129. doi: 10.1093/jmcb/mjx041.

Abstract

Large-intergenic noncoding RNAs (lincRNAs) cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and gene transcription remain mostly unknown. Here, we identified that a lincRNA (linc1614), occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 served as a specific partner of core factor Sox2 in maintaining pluripotency, primarily by mediating the function of Sox2 in the repression of developmental genes. Moreover, Ezh2, an essential subunit of polycomb repressive complex 2 (PRC2), physically interacted with linc1614 and contributed to lincRNA-mediated transcriptional silencing. Thus, we propose that the interplay of linc1614 with Sox2 implicates this lincRNA as a recruitment platform that mediates transcriptional silencing by guiding the PRC2 complex to the loci of developmental genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellular Reprogramming
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Gene Expression Regulation, Developmental*
  • Mice
  • Polycomb Repressive Complex 2 / genetics*
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • SOXB1 Transcription Factors / genetics*

Substances

  • RNA, Long Noncoding
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 2