Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19

Elife. 2020 Sep 1:9:e58675. doi: 10.7554/eLife.58675.

Abstract

The Polycomb repressive complex 2 (PRC2) is a multicomponent histone H3K27 methyltransferase complex, best known for silencing the Hox genes during embryonic development. The Polycomb-like proteins PHF1, MTF2, and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3 in vitro. However, some other studies suggest that PHF1 and PHF19 co-localize with the H3K27me3 mark but not H3K36me3 in cells. Here, we provide further evidence that PHF1 co-localizes with H3t in testis and its Tudor domain preferentially binds to H3tK27me3 over canonical H3K27me3 in vitro. Our complex structures of the Tudor domains of PHF1 and PHF19 with H3tK27me3 shed light on the molecular basis for preferential recognition of H3tK27me3 by PHF1 and PHF19 over canonical H3K27me3, implicating that H3tK27me3 might be a physiological ligand of PHF1/19.

Keywords: PHF1; Polycomb; Tudor; chromatin; epigenetics; histone methylation; human; molecular biophysics; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • HEK293 Cells
  • Histones / chemistry*
  • Histones / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polycomb Repressive Complex 2 / chemistry
  • Polycomb Repressive Complex 2 / metabolism
  • Polycomb-Group Proteins / chemistry*
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism
  • Protein Binding
  • Testis / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tudor Domain

Substances

  • DNA-Binding Proteins
  • Histones
  • PHF1 protein, human
  • PHF19 protein, human
  • Phf1 protein, mouse
  • Phf19 protein, mouse
  • Polycomb-Group Proteins
  • Transcription Factors
  • Polycomb Repressive Complex 2