Bai, G. (BMEB) – Long-read single-molecule chromatin architecture and its role in transcriptome regulation

Sequencing technologies have revolutionized our understanding of biology, yet many existing methods require fragmentation of DNA or RNA, fundamentally limiting our ability to study these molecules in their native, intact forms. Long-read sequencing overcomes this constraint by enabling the sequencing of long, single-molecule native DNA and RNA, providing simultaneous access to both sequence and base modifications that reflect epigenetic state. This capability has already yielded landmark achievements, including the first complete, gapless human genome assembly. Yet while our ability to decode genomic sequence has advanced dramatically, how chromatin structure shapes a cell’s transcriptome remains poorly understood. My thesis addresses this gap through three aims. First, I co-developed a novel long-read approach for profiling chromatin accessibility at single-molecule resolution using the small molecule angelicin. Second, I characterized how long-range chromatin states are associated with RNA processing and transcription, leveraging multi-omic long-read data in yeast. Third, I incorporate chromatin data into sequence-to-function deep learning models to interpret the mechanistic contribution of chromatin state to RNA processing. Together, these aims establish a new framework for studying the relationship between epigenetic state and transcriptome regulation at a resolution not previously possible.

Event Host: Gali Bai, Ph.D. Candidate, Biomolecular Engineering & Bioinformatics

Advisor: Angela Brooks

Zoom Meeting ID: 940 6201 8397

Passcode: 700963