BRD4 Interacts With NIPBL and BRD4 Is Mutated in a Cornelia De Lange-like Syndrome

Nat Genet. 2018 Mar;50(3):329-332. doi: 10.1038/s41588-018-0042-y. Epub 2018 Jan 29.

Abstract

We found that the clinical phenotype associated with BRD4 haploinsufficiency overlapped with that of Cornelia de Lange syndrome (CdLS), which is most often caused by mutation of NIPBL. More typical CdLS was observed with a de novo BRD4 missense variant, which retained the ability to coimmunoprecipitate with NIPBL, but bound poorly to acetylated histones. BRD4 and NIPBL displayed correlated binding at super-enhancers and appeared to co-regulate developmental gene expression.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Cycle Proteins
  • Cells, Cultured
  • Child
  • Child, Preschool
  • De Lange Syndrome / genetics*
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Haploinsufficiency
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation, Missense*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Pedigree
  • Phenotype
  • Protein Binding
  • Proteins / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • NIPBL protein, human
  • Nuclear Proteins
  • Proteins
  • Transcription Factors