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Mapping the Establishment of Heterochromatin Domains During Early Drosophila Embryogenesis

Award Number: F31HD121399
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Mapping the Establishment of Heterochromatin Domains During Early Drosophila Embryogenesis - PROJECT SUMMARY An essential period of embryonic development is the organization of the genome into active and repressive chromatin states to ensure proper gene regulation and cellular differentiation. Constitutive heterochromatin is one of these states that forms dense nuclear domains that ensures genome stability and accurate chromosome segregation during division. Decades of research has demonstrated that this feature is conserved across species and disruptions to this process can lead to developmental delays, chromosomal instability, and have been linked to congenital disorders, including autism spectrum disorders and Kleefstra syndrome. Across eukaryotes, constitutive heterochromatin is characterized by di- or tri-methylation of histone H3 lysine 9 (H3K9me2/3). Two conserved histone methyltransferases (HMTs), Egg/SetDB1 and Su(var)3-9, deposit methyl groups during early embryonic development. However, how these enzymes interact with specific genomic regions to establish heterochromatin domains during embryonic development remains unclear. Recent reports observe the localization of HMTs at regions that are repetitive, a distinct feature of heterochromatin domains. This line of evidence suggests a potential site-specific target for HMTs. This project aims to fill this gap by tracking the spatiotemporal enrichment of H3K9me3 in early embryogenesis in Drosophila. Therefore, the central hypothesis is that heterochromatin formation is initiated at specific nucleation sites by Egg and expanded by Su(var)3-9, facilitating domain expansion. To test this hypothesis, I will leverage a novel long-read sequencing approach that uses a targeted protein-DNA mapping method to profile the enrichment of H3K9me3. My approach to support my hypothesis is by characterizing H3K9me3 enrichment across staged embryonic nuclear cycles to define spatiotemporal dynamics (Aim 1) and analyzing H3K9me3 enrichment in Egg and Su(var)3-9 mutants to dissect their specific roles (Aim 2). These experiments will provide fundamental insights into epigenetic regulation of heterochromatin formation in early embryogenesis. By integrating innovative sequencing technologies with a well-characterized model system, this study will advance our understanding of epigenetic mechanisms governing early embryogenesis. This research will take place in the Karpen Lab at UC Berkeley, which provides an ideal environment for this work, offering expertise in nuclear organization and epigenomics. As part of my training plan, I will gain experience in long-read sequencing technologies, mentor undergraduate students, present my research at conferences, and participate in coursework and professional development to support my career in developmental epigenetics. Ultimately, I find myself in a conducive environment to pursue novel insights into how heterochromatin is first established during embryonic development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $48,395 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Child Health and Human Development Extramural Research	000	1	3/25/2026	NEW	$48,395
														Subtotal = $48,395

Grand Total All Awards = $48,395

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Mapping the Establishment of Heterochromatin Domains During Early Drosophila Embryogenesis

Award Number: F31HD121399

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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