Reprogramming chromatin

Crit Rev Biochem Mol Biol. 2012 Sep;47(5):464-82. doi: 10.3109/10409238.2012.697125. Epub 2012 Jul 3.

Abstract

Cellular reprogramming involves the artificial dedifferentiation of somatic cells to a pluripotent state. When affected by overexpressing specific transcription factors, the process is highly inefficient, as only 0.1-1% of cells typically undergo the transformation. This low efficiency has been attributed to high kinetic barriers that affect all cells equally and can only be overcome by rare stochastic events. The barriers to reprogramming are likely to involve transformations of chromatin state because (i) inhibitors of chromatin-modifying enzymes can enhance the efficiency of reprogramming and (ii) knockdown or knock-out of chromatin-modifying enzymes can lower the efficiency of reprogramming. Here, we review the relationship between chromatin state transformations (chromatin reprogramming) and cellular reprogramming, with an emphasis on transcription factors, chromatin remodeling factors, histone modifications and DNA methylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Cell Differentiation*
  • Cellular Reprogramming*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA Methylation
  • Enzyme Inhibitors / metabolism
  • Gene Expression Regulation, Developmental*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Transcription Factors
  • Transcription, Genetic

Substances

  • Chromatin
  • Enzyme Inhibitors
  • Histones
  • Transcription Factors