Analysis of Local Chromatin States Reveals Gene Transcription Potential during Mouse Neural Progenitor Cell Differentiation

Cell Rep. 2020 Jul 28;32(4):107953. doi: 10.1016/j.celrep.2020.107953.

Abstract

Chromatin dynamics play a critical role in cell fate determination and maintenance by regulating the expression of genes essential for development and differentiation. In mouse embryonic stem cells (mESCs), maintenance of pluripotency coincides with a poised chromatin state containing active and repressive histone modifications. However, the structural features of poised chromatin are largely uncharacterized. By adopting mild time-course MNase-seq with computational analysis, the low-compact chromatin in mESCs is featured in two groups: one in more open regions, corresponding to an active state, and the other enriched with bivalent histone modifications, considered the poised state. A parameter called the chromatin opening potential index (COPI) is also devised to quantify the transcription potential based on the dynamic changes of MNase-seq signals at promoter regions. Use of COPI provides effective prediction of gene activation potential and, more importantly, reveals a few developmental factors essential for mouse neural progenitor cell (NPC) differentiation.

Keywords: MNase-seq; cell fate; poised chromatin; transcription potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Lineage / genetics
  • Chromatin / genetics*
  • Epigenesis, Genetic / genetics
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Histone Code / genetics
  • Histones / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / metabolism
  • Neural Stem Cells / metabolism*
  • Promoter Regions, Genetic / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics

Substances

  • Chromatin
  • Histones
  • Transcription Factors