Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 1 of 1
Full-Text Articles in Medicine and Health Sciences
Inability To Switch From Arid1a-Baf To Arid1b-Baf Impairs Exit From Pluripotency And Commitment Towards Neural Crest Formation In Arid1b-Related Neurodevelopmental Disorders, Luca Pagliaroli, Patrizia Porazzi, Alyxandra T Curtis, Chiara Scopa, Harald M M Mikkers, Christian Freund, Lucia Daxinger, Sandra Deliard, Sarah A Welsh, Sarah Offley, Connor A Ott, Bruno Calabretta, Samantha A Brugmann, Gijs W E Santen, Marco Trizzino
Inability To Switch From Arid1a-Baf To Arid1b-Baf Impairs Exit From Pluripotency And Commitment Towards Neural Crest Formation In Arid1b-Related Neurodevelopmental Disorders, Luca Pagliaroli, Patrizia Porazzi, Alyxandra T Curtis, Chiara Scopa, Harald M M Mikkers, Christian Freund, Lucia Daxinger, Sandra Deliard, Sarah A Welsh, Sarah Offley, Connor A Ott, Bruno Calabretta, Samantha A Brugmann, Gijs W E Santen, Marco Trizzino
Department of Biochemistry and Molecular Biology Faculty Papers
Subunit switches in the BAF chromatin remodeler are essential during development. ARID1B and its paralog ARID1A encode for mutually exclusive BAF subunits. De novo ARID1B haploinsufficient mutations cause neurodevelopmental disorders, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we leveraged ARID1B+/- Coffin-Siris patient-derived iPSCs and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF). ARID1B-BAF regulates exit from pluripotency and lineage commitment by attenuating thousands of enhancers and genes of …