ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters

Nat Commun. 2015 Feb 3;2:6186. doi: 10.1038/ncomms7186.

Abstract

Chromatin interactions connect distal regulatory elements to target gene promoters guiding stimulus- and lineage-specific transcription. Few factors securing chromatin interactions have so far been identified. Here, by integrating chromatin interaction maps with the large collection of transcription factor-binding profiles provided by the ENCODE project, we demonstrate that the zinc-finger protein ZNF143 preferentially occupies anchors of chromatin interactions connecting promoters with distal regulatory elements. It binds directly to promoters and associates with lineage-specific chromatin interactions and gene expression. Silencing ZNF143 or modulating its DNA-binding affinity using single-nucleotide polymorphisms (SNPs) as a surrogate of site-directed mutagenesis reveals the sequence dependency of chromatin interactions at gene promoters. We also find that chromatin interactions alone do not regulate gene expression. Together, our results identify ZNF143 as a novel chromatin-looping factor that contributes to the architectural foundation of the genome by providing sequence specificity at promoters connected with distal regulatory elements.

Publication types

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

MeSH terms

  • Binding Sites
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Humans
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic*
  • Regulatory Sequences, Nucleic Acid
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Chromatin
  • Trans-Activators
  • ZNF143 protein, human