Inheritance and Reprogramming of Maternal Chromatin during Zebrafish Maternal Zygotic Transition.

/Abstract: Inheritance and Reprogramming of Maternal Chromatin during Zebrafish Maternal Zygotic Transition Zygotic genome activation (ZGA) is a pivotal event during the maternal-to-zygotic transition (MZT), the developmental period shortly after fertilization when gametic genomes undergo reprogramming. Epigenetic reprogramming of the parental genomes is essential to prepare the zygotic genome for transcription activation. Additionally, the localization of transcription machinery such as transcription factors and RNA Polymerase II to zygotic genes plays a crucial role in their precise transcriptional activation. However, it has remained unknown how maternally provided transcription repressors function to prevent precocious zygotic transcription activation prior to ZGA. Using the genomic and molecular approaches, we have discovered certain loci may function as transcription repressors potentially via sequestering transcription machinery including transcription factors and RNA Polymerase II from developmental genes. During the lead-up to ZGA, the chromatin accessibility at these loci is drastically decreased and this decrease coincides with increased accessibility and subsequent nascent transcription at developmental genes. I also found that the decrease in accessibility of these loci is associated with heterochromatin establishment at these loci. I hypothesize that specific loci function as a sink and sequester transcription machinery including RNA Polymerase II to silence zygotic gene transcription until the epigenetic repression of these loci leads to the release of RNA Polymerase II to drive nascent transcription at zygotic genes. Using a combination of genomic, molecular, and imaging approaches, I will use mutants that inherit these loci with accessibility lower than that in wildtype and mutants that fail to silence these loci at ZGA to investigate their functions in the regulation of ZGA timing. These studies would demonstrate transcription machinery sequestration as a novel mechanism of ZGA regulation. Project Number: 1F30HD117533-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Duy Nguyen | Institution: UNIVERSITY OF ROCHESTER, ROCHESTER, NY | Award Amount: $54,538 | Activity Code: F30 | Study Section: Special Emphasis Panel[ZRG1 F08-L (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1F30HD11753301A1