BME 280B Seminar: Gali Bai & David Haussler
Presenter 1: Gali Bai, BME/PBSE Doctoral Candidate, Brooks Lab, UC Santa Cruz
Title 1: Dissecting the contribution of chromatin accessibility to RNA transcription and processing with long-read sequencing
Description: Although all cells in an organism share the same genomic sequence, transcriptional programs vary dramatically across cell types. This diversity is governed by epigenetic regulation involving the coordinated activities of chromatin remodelers, histone modifiers, and histone chaperones that precisely modulate chromatin accessibility. While previous studies have shown that chromatin accessibility at DNase I–hypersensitive sites such as promoters and enhancers is closely associated with gene expression, much less is known about how chromatin influences transcription and RNA processing. To study how chromatin regulates RNA processing, we perturbed yeast chromatin accessibility by deleting two highly conserved chromatin remodelers ISW1 and CHD1. With Oxford Nanopore long-read sequencing, we profiled nascent RNA, full-length mRNA, and chromatin fibers in wild-type and chd1 isw1 double-mutant yeast cells. Loss of ISW1 and CHD1 led to increased chromatin accessibility within intragenic regions, accompanied by aberrant transcription initiation. Leveraging long-read data, we associated distinct chromatin states with specific RNA processing events and isoform expression outcomes. Despite a similar level of chromatin perturbations across the genome, genes with low baseline expression showed extensive transcriptional reprogramming, whereas highly expressed genes remained largely unaffected. These discrepancies can be partially explained by differences in the enrichment of transcription initiation motifs. In intron-containing genes, loss of ISW1 and CHD1 reduced splicing efficiency and increased intron retention, likely due to disrupted RNAPII elongation in the double mutant. Together, our findings highlight the crucial role of ATP-dependent chromatin remodelers in maintaining nucleosome organization and coordinating co-transcriptional RNA processing.
Presenter 2: David Haussler, Distinguished Professor, UC Santa Cruz
Title 2: Brain Organoids
Bio: Haussler received his PhD in computer science from the University of Colorado at Boulder. He is a member of the National Academy of Sciences, the National Academy of Engineering, the American Academy of Arts and Sciences and a fellow of AAAS and AAAI. He has won a number of awards, including the 2015 Dan David Prize, the 2011 Weldon Memorial Prize from University of Oxford, the 2009 ASHG Curt Stern Award in Human Genetics, the 2008 Senior Scientist Accomplishment Award from the International Society for Computational Biology, the 2005 Dickson Prize for Science from Carnegie Mellon University, and the 2003 ACM/AAAI Allen Newell Award in Artificial Intelligence.
Hosted by: Professor Josh Stuart, BME Department
