Cohesin: an emerging master regulator at the heart of cardiac development

Abstract

Cohesins are ATPase complexes that play central roles in cellular processes such as chromosome division, DNA repair, and gene expression. Cohesinopathies arise from mutations in cohesin proteins, or cohesin complex regulators, and encompass a family of related developmental disorders that present with a range of severe birth defects, affect many different physiological systems, and often lead to embryonic fatality. Treatments for cohesinopathies are limited, in large part due to the lack in understanding of cohesin biology. Thus, characterizing the signaling networks that lie upstream and downstream of cohesin-dependent pathways remains clinically relevant. Here, we highlight alterations in cohesins, and cohesin regulators, that result in cohesinopathies with a focus on cardiac defects. In addition, we suggest a novel and more unifying view regarding the mechanisms through which cohesinopathy-based heart defects may arise.

Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature

“…Pathogenic variants most likely cause CdLS in one of the cohesin complex genes, including NIPBL (NIPBL cohesin loading factor-OMIM:608667), which accounts for about 50-60% of cases; SMC1A (structural maintenance of chromosomes protein 1A-OMIM:300040) and HDAC8 (histone deacetylase 8-OMIM:300269), linked to the X chromosome; and SMC3 (structural maintenance of chromosomes 3-OMIM:606062) and RAD21 (RAD21 cohesin complex component-OMIM:606462). They can be spontaneous, autosomal dominant, or X-recessive [2,6]. Some of the newly identified genes that contribute to the understanding of CdLS include ANKRD11 (ankyrin repeat domain-containing protein 11-OMIM:611192), EP300 (interacting inhibitor of differentiation 1-OMIM: 605894), AFF4 (alf transcription elongation factor 4-OMIM:604417), TAF1 (rna polymerase ii, tata box-binding protein-OMIM: 313650), ARCN1 (coatomer protein complex-OMIM: 600820), ARID1B (at-rich interaction domain-containing protein 1b-OMIM: 614556), ASXL2 (asxl transcriptional regulator 2-OMIM: 612991), and BRD4 (bromodomain-containing protein 4-OMIM:608749) [3,7].…”

Advancing the Clinical and Molecular Understanding of Cornelia De Lange Syndrome: A Multidisciplinary Pediatrics Case Series and Review of Literature

“…2 chromosome; and SMC3 and RAD21. Mutations can be spontaneous, autosomal dominant, or Xrecessive [2,4]. However, the diagnosis is made clinically [1,2].…”