ARID1A spatially partitions interphase chromosomes

Sci Adv. 2019 May 22;5(5):eaaw5294. doi: 10.1126/sciadv.aaw5294. eCollection 2019 May.


ARID1A, a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex, localizes to both promoters and enhancers to influence transcription. However, the role of ARID1A in higher-order spatial chromosome partitioning and genome organization is unknown. Here, we show that ARID1A spatially partitions interphase chromosomes and regulates higher-order genome organization. The SWI/SNF complex interacts with condensin II, and they display significant colocalizations at enhancers. ARID1A knockout drives the redistribution of condensin II preferentially at enhancers, which positively correlates with changes in transcription. ARID1A and condensin II contribute to transcriptionally inactive B-compartment formation, while ARID1A weakens the border strength of topologically associated domains. Condensin II redistribution induced by ARID1A knockout positively correlates with chromosome sizes, which negatively correlates with interchromosomal interactions. ARID1A loss increases the trans interactions of small chromosomes, which was validated by three-dimensional interphase chromosome painting. These results demonstrate that ARID1A is important for large-scale genome folding and spatially partitions interphase chromosomes.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Binding Sites
  • Cell Line, Tumor
  • Chromatin / chemistry
  • Chromosomes / ultrastructure*
  • Cluster Analysis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Enhancer Elements, Genetic
  • Gene Expression Profiling
  • Humans
  • Interphase / genetics*
  • Multiprotein Complexes / chemistry
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA-Seq
  • Serine Endopeptidases / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • ARID1A protein, human
  • Chromatin
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Transcription Factors
  • condensin complexes
  • PRSS27 protein, human
  • Serine Endopeptidases
  • Adenosine Triphosphatases