BibTex format
@article{Barnada:2024:10.1016/j.ajhg.2024.07.022,
author = {Barnada, SM and Giner, de Gracia A and Morenilla-Palao, C and López-Cascales, MT and Scopa, C and Waltrich, FJ and Mikkers, HMM and Cicardi, ME and Karlin, J and Trotti, D and Peterson, KA and Brugmann, SA and Santen, GWE and McMahon, SB and Herrera, E and Trizzino, M},
doi = {10.1016/j.ajhg.2024.07.022},
journal = {Am J Hum Genet},
title = {ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification.},
url = {http://dx.doi.org/10.1016/j.ajhg.2024.07.022},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The BAF chromatin remodeler regulates lineage commitment including cranial neural crest cell (CNCC) specification. Variants in BAF subunits cause Coffin-Siris syndrome (CSS), a congenital disorder characterized by coarse craniofacial features and intellectual disability. Approximately 50% of individuals with CSS harbor variants in one of the mutually exclusive BAF subunits, ARID1A/ARID1B. While Arid1a deletion in mouse neural crest causes severe craniofacial phenotypes, little is known about the role of ARID1A in CNCC specification. Using CSS-patient-derived ARID1A+/- induced pluripotent stem cells to model CNCC specification, we discovered that ARID1A-haploinsufficiency impairs epithelial-to-mesenchymal transition (EMT), a process necessary for CNCC delamination and migration from the neural tube. Furthermore, wild-type ARID1A-BAF regulates enhancers associated with EMT genes. ARID1A-BAF binding at these enhancers is impaired in heterozygotes while binding at promoters is unaffected. At the sequence level, these EMT enhancers contain binding motifs for ZIC2, and ZIC2 binding at these sites is ARID1A-dependent. When excluded from EMT enhancers, ZIC2 relocates to neuronal enhancers, triggering aberrant neuronal gene activation. In mice, deletion of Zic2 impairs NCC delamination, while ZIC2 overexpression in chick embryos at post-migratory neural crest stages elicits ectopic delamination from the neural tube. These findings reveal an essential ARID1A-ZIC2 axis essential for EMT and CNCC delamination.
AU - Barnada,SM
AU - Giner,de Gracia A
AU - Morenilla-Palao,C
AU - López-Cascales,MT
AU - Scopa,C
AU - Waltrich,FJ
AU - Mikkers,HMM
AU - Cicardi,ME
AU - Karlin,J
AU - Trotti,D
AU - Peterson,KA
AU - Brugmann,SA
AU - Santen,GWE
AU - McMahon,SB
AU - Herrera,E
AU - Trizzino,M
DO - 10.1016/j.ajhg.2024.07.022
PY - 2024///
TI - ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification.
T2 - Am J Hum Genet
UR - http://dx.doi.org/10.1016/j.ajhg.2024.07.022
UR - https://www.ncbi.nlm.nih.gov/pubmed/39226899
ER -