Fig. 4: Cornelia de Lange syndrome is a cohesinopathy.
From: Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement
Cornelia de Lange syndrome (CdLS) is caused by genetic variants that affect subunits or regulators of the cohesin complex. The structural core components double-strand break repair protein rad21 homologue (RAD21), structural maintenance of chromosomes protein 1A (SMC1A) and SMC3 of cohesin are thought to form a tripartite ring entrapping chromatids. In humans, cohesin subunit SA1 (STAG1), STAG2 or STAG3 directly attach to the ring and form part of the core complex. Nipped-B-like protein (NIPBL) and MAU2 chromatid cohesion factor homologue form a heterodimeric complex named kollerin that is required for cohesin loading onto DNA, and in which bromodomain-containing protein 4 (BRD4) interacts with NIPBL. Histone deacetylase 8 (HDAC8) regulates the cohesin complex release from chromatin by deacetylating SMC3. The functional interaction of ankyrin repeat domain-containing protein 11 (ANKRD11) with cohesin is under study but is currently unknown. Ac, acetyl group; AFF4, AF4/FMR2 family member 4; EF, elongation factor; RNAPII, RNA polymerase II; TF, transcription factor.
