Interplay Between Transcription and ATP-dependent Chromatin Remodeling for Genome Regulation

(RPL Brahma, Sandipan: "Interplay Between Transcription and ATP-dependent Chromatin Remodeling for Genome Regulation") Epigenetic control of gene expression is intricately linked to the organization of chromosomal nucleosomes and regulatory proteins within chromatin, which governs DNA accessibility and spatial arrangement within folded chromatin structures. Dysregulation of these processes contributes to developmental disorders, neurological conditions, and cancer. Despite recent advancements, understanding the causal relationships between pivotal chromatin regulatory processes, such as ATP-dependent chromatin remodeling, transcription, and 3D genome organization, remains to be discovered, mainly due to technological limitations in measuring protein cooperativity and dynamics across genomic scales. To address these challenges, we propose to leverage our expertise in cutting-edge structural and functional epigenomics technologies and advanced biochemistry approaches to uncover the dynamic interplay between basal transcription machinery and chromatin remodelers in establishing cell-type-specific chromatin structures. Specifically, our aims are to 1) determine how transcription influences chromatin landscapes, 2) dissect how ATP-dependent nucleosome remodelers collaborate with DNA-sequence-specific transcription factors genome-wide, and 3) investigate the roles of ATP-dependent nucleosome remodeling and transcription in shaping the 3D genome. The outcomes of this study have the potential to transform our understanding of fundamental mechanisms of gene regulation with novel concepts as well as new methodologies. Additionally, our findings will shed light on disease mechanisms associated with chromatin regulator mutations and may offer insights into potential targeted therapeutic strategies. Project Number: 5P20GM121316-08 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Sandipan Brahma | Institution: UNIVERSITY OF NEBRASKA MEDICAL CENTER, OMAHA, NE | Award Amount: $280,905 | Activity Code: P20 | Study Section: ZGM1-RCB-4(C2) View on NIH RePORTER: https://reporter.nih.gov/project-details/11456533