Date: Friday, April 7, 2017
Time: 12:00pm – 1:00pm
Speaker: Ashley Watson, Ph.D.
Affiliation: Postdoctoral Fellow, Dr. Li-Huei Tsai’s laboratory, Picower Institute for Learning and Memory
Talk Title: Chromatin organization and function in the molecular etiology of autism
Abstract: Spatial organization of the genome in three dimensions (3D) is an important aspect of tissue-specific developmental transcriptional regulation that involves chromatin remodeling factors, architectural proteins, and interactions between distal regulatory elements. The zinc finger protein CTCF has emerged as a critical factor in mediating long-range chromatin interactions to regulate transcription. Recent exome sequencing of autism spectrum disorder (ASD) patients identified multiple haploinsufficient mutations in the zinc finger DNA-binding domain of CTCF, suggesting that alterations in CTCF binding may contribute to abnormal neurodevelopment and disease pathogenesis. To investigate the relationship between CTCF-mediated chromatin topology and transcriptional regulation, we generated isogenic human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) harboring autism spectrum disorder (ASD)-linked CTCF mutation. I will present transcriptomic and epigenomic data to support the role of CTCF in orchestrating transcriptional programs essential for neurodevelopment. These findings shed light on the consequence of specific ASD-linked mutations and have important implications for transcriptional regulation via 3D chromatin organization in neurodevelopment.