PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription

Mol Cell. 2015 Sep 17;59(6):984-97. doi: 10.1016/j.molcel.2015.07.019. Epub 2015 Aug 27.

Abstract

Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and its co-factor CTCF. They not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina. Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCCTC-Binding Factor
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / genetics*
  • Chromatin Immunoprecipitation
  • Circadian Rhythm
  • Embryoid Bodies / enzymology
  • Epistasis, Genetic
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • HCT116 Cells
  • Human Embryonic Stem Cells / enzymology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nuclear Lamina / metabolism
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Repressor Proteins / metabolism*
  • Transcription, Genetic*

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Cell Cycle Proteins
  • Chromatin
  • H19 long non-coding RNA
  • Membrane Proteins
  • PARD3 protein, human
  • RNA, Long Noncoding
  • Repressor Proteins
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases

Associated data

  • GEO/GSE26880
  • GEO/GSE58534