Chromatin regulation: how complex does it get?

Epigenetics. 2014 Nov;9(11):1485-95. doi: 10.4161/15592294.2014.971580.


Gene transcription is tightly regulated at different levels to ensure that the transcriptome of the cell is appropriate for developmental stage and cell type. The chromatin state in which a gene is embedded determines its expression level to a large extent. Activation or repression of transcription is typically accomplished by the recruitment of chromatin-associated multisubunit protein complexes that combine several molecular tools, such as histone-binding and chromatin-modifying activities. Recent biochemical purifications of such complexes have revealed a substantial diversity. On the one hand, complexes that were thought to be unique have been revealed to be part of large complex families. On the other hand, protein subunits that were thought to only exist in separate complexes have been shown to coexist in novel assemblies. In this review we discuss our current knowledge of repressor complexes that contain MBT domain proteins and/or the CoREST co-repressor and use them as a paradigm to illustrate the unexpected heterogeneity and tool sharing of chromatin regulating protein complexes. These recent insights also challenge the ways we define and think about protein complexes in general.

Keywords: ATP, adenosine triphosphate; BAP, brahma associated protein; BHC80, BRAF-histone deacetylase complex 80; BRG1, brahma Related Gene 1; CHD, chromo domain helicase DNA binding; CoREST; CoREST REST, corepressor; DNA, deoxyribonucleic acid; DNMT, DNA methyltransferase; DP-1, dimerization partner 1; E2F, E2 transcription Factor; ELM2, EGL-27 and MTA1 homology 2; ES cell, embryonic stem cells; H, histone; HDAC, histone deacetylas; HMTase, histone methylase; HP1, heterochromatin protein 1; K, lysine; L3MBTL, lethal 3 malignant brain tumor-like; LINT, l(3)mbt interacting; LSD1, lysine-specific demethylase 1; Lint-1, l(3)mbt interacting 1; MBT protein; MBT, malignant brain tumor; MBTS, malignant brain tumor signature; NPA1, nucleosome assembly protein; NRSF, neural-restrictive silencing factor; NuRD, nucleosome remodeling and deacetylase; PBAP, polybromo-associated BAP; PHD, plant homeo domain; PRC1, polycomb repressive complex 1; PRE, polycomb responsive element; Pc, polycomb; PcG, polycomb group; Ph, polyhomeotic; Pho, pleiohomeotic; PhoRC, Pho repressive complex; Psc, posterior sex combs; RB, retinoblastoma; REST, repressor element 1 silencing transcription factor; RNA, ribonucleic acid; Rpd3, reduced potassium dependency 3; SANT, SWI/ADA2/N-CoR/TFIIIB; SCML, sex combs on midleg-like; SLC, SFMBT1, LSD1, CoREST; SWH, Salvador-Warts-Hippo; SWI/SNF, switching defective/sucrose non-fermenting; Sce, sex combs extra; Scm, sex combs on midleg; Sfmbt, Scm-related gene containing 4 mbt domains; TSS, transcription start site; YY1, ying-yang 1; ZNF, zinc finger; complex family; dL(3)mbt, Drosophila Lethal 3 malignant brain tumor; hBRM, human Brahma; l(3)mbt, lethal 3 malignant brain tumor; protein complex; transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Co-Repressor Proteins / genetics
  • Co-Repressor Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / metabolism
  • Evolution, Molecular
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Protein Structure, Tertiary


  • Chromatin
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • L3MBTL3 protein, human
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • RCOR1 protein, human