Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance

Stem Cell Reports. 2018 Feb 13;10(2):627-641. doi: 10.1016/j.stemcr.2017.12.016.

Abstract

The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongation-associated histone H3.3 enrichment. Depletion of heterochromatin anchoring protein SENP7 increased reprogramming efficiency to a similar extent as HP1γ, indicating the importance of HP1γ release from chromatin for pluripotency acquisition. HP1γ interacted with OCT4 and DPPA4 in HP1α and HP1β knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell (ESC) lines. HP1α and HP1γ complexes in ESCs differed in association with histones, the histone chaperone CAF1 complex, and specific components of chromatin-modifying complexes such as DPY30, implying distinct functional contributions. Taken together, our results reveal the complex contribution of the HP1 proteins to pluripotency.

Keywords: Dppa4; H3.3; H3K9M; HP1α knockout; HP1β knockout; HP1γ knockout; Senp7; iPSC; pluripotency; reprogramming.

Publication types

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

MeSH terms

  • Animals
  • Cellular Reprogramming / genetics*
  • Chromatin / chemistry
  • Chromatin / genetics*
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Endopeptidases / chemistry
  • Endopeptidases / genetics
  • Exoribonucleases
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / genetics
  • Histones / genetics
  • Humans
  • Induced Pluripotent Stem Cells / chemistry*
  • Induced Pluripotent Stem Cells / cytology
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics*
  • Nuclear Proteins / genetics
  • Octamer Transcription Factor-3 / chemistry
  • Octamer Transcription Factor-3 / genetics
  • Proteins / chemistry
  • Proteins / genetics
  • Repressor Proteins
  • Ribonucleases
  • Transcription Factors

Substances

  • CBX1 protein, human
  • CBX5 protein, human
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Dppa4 protein, mouse
  • Dpy30 protein, mouse
  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Proteins
  • Repressor Proteins
  • Transcription Factors
  • Chromobox Protein Homolog 5
  • Histone-Lysine N-Methyltransferase
  • Cnot7 protein, mouse
  • Exoribonucleases
  • Ribonucleases
  • Endopeptidases
  • SENP7 protein, mouse