Cornelia De Lange Syndrome Mutations in NIPBL Can Impair Cohesin-mediated DNA Loop Extrusion

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Apr 27

PMID 35476527

Authors

Melanie Panarotto

Iain F Davidson

Gabriele Litos

Alexander Schleiffer

Jan-Michael Peters

Affiliations

Soon will be listed here.

Abstract

Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers.

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