Mutant cohesin affects RNA polymerase II regulation in Cornelia de Lange syndrome

Linda Mannini, Fabien C Lamaze, Francesco Cucco, Clelia Amato, Valentina Quarantotti, Ilaria M Rizzo, Ian D Krantz, Steve Bilodeau, Antonio Musio

Research output: Contribution to journalArticlepeer-review


In addition to its role in sister chromatid cohesion, genome stability and integrity, the cohesin complex is involved in gene transcription. Mutations in core cohesin subunits SMC1A, SMC3 and RAD21, or their regulators NIPBL and HDAC8, cause Cornelia de Lange syndrome (CdLS). Recent evidence reveals that gene expression dysregulation could be the underlying mechanism for CdLS. These findings raise intriguing questions regarding the potential role of cohesin-mediated transcriptional control and pathogenesis. Here, we identified numerous dysregulated genes occupied by cohesin by combining the transcriptome of CdLS cell lines carrying mutations in SMC1A gene and ChIP-Seq data. Genome-wide analyses show that genes changing in expression are enriched for cohesin-binding. In addition, our results indicate that mutant cohesin impairs both RNA polymerase II (Pol II) transcription initiation at promoters and elongation in the gene body. These findings highlight the pivotal role of cohesin in transcriptional regulation and provide an explanation for the typical gene dysregulation observed in CdLS patients.

Original languageEnglish
Pages (from-to)16803
JournalScientific Reports
Publication statusPublished - 19 Nov 2015


  • Cell Cycle Proteins/genetics
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone/genetics
  • De Lange Syndrome/genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human
  • Humans
  • Mutation/genetics
  • Phosphorylation
  • Promoter Regions, Genetic/genetics
  • Protein Binding
  • RNA Polymerase II/metabolism
  • Transcription, Genetic


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