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Regulation and function of H2A.Z during the mid-blastula transition

Award Number: R01HD105489
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/04/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Regulation and function of H2A.Z during the mid-blastula transition - PROJECT SUMMARY Developmental progression from cleavage phase to gastrulation occurs during the mid-blastula transition (MBT). This transition coincides with several critical events, including maternal to zygotic transition, zygotic genome activation (ZGA), and stem cell formation. How the zygotic genome becomes activate and how proper developmental timing is regulated are critical unknowns in biology. Recent data in zebrafish and Drosophila indicate that these processes are highly sensitive to the levels a particular histone, the histone variant H2A.Z (H2Av in Drosophila). However, it remains largely unknown why altered H2A.Z levels disrupt MBT events and how the embryo ordinarily assures that the correct amount of H2A.Z is incorporated into chromatin. Preliminary observations indicate that in both species a subset of zygotic genes is prematurely activated when H2A.Z levels are elevated. A combination of genomics approaches and expression analysis of candidate genes will be used to determine the temporal pattern of gene activation in embryos with up- or downregulated nuclear H2A.Z levels. It will also be tested to what extent the observed changes are due to chromatin associated factors (in particular the pattern of H2A.Z distribution across the genome) and epigenetic marks. Use of the two distinct model systems will reveal to what extent the underlying mechanisms are conserved between vertebrates and insects. In Drosophila, it is known that H2A.Z levels in the nucleus can be regulated by the H2A.Z binding protein Jabba that sequesters H2A.Z in the cytoplasm, a process active during the time of the MBT. Preliminary studies have led to the hypothesis that a different H2A.Z-binding protein plays an analogous role in zebrafish. This hypothesis will be tested using live imaging, embryo injections, and structure-function analysis. Successful completion of this project will define the role of H2A.Z in controlling gene expression patterns and in cellular programming during one of the most crucial periods of development, the mid- blastula transition.


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 = $331,100 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Child Health and Human Development Extramural Research	000	5	3/5/2026	NON-COMPETING CONTINUATION	$331,100
														Subtotal = $331,100

Issue Date FY: 2025 ( Subtotal = $331,100 )
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Child Health and Human Development Extramural Research	000	4	4/4/2025	NON-COMPETING CONTINUATION	$331,100
														Subtotal = $331,100

Issue Date FY: 2024 ( Subtotal = $327,789 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Child Health and Human Development Extramural Research	000	3	3/18/2024	NON-COMPETING CONTINUATION	$297,990
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Child Health and Human Development Extramural Research	001	3	5/6/2024	NON-COMPETING CONTINUATION	$29,799
														Subtotal = $327,789

Issue Date FY: 2023 ( Subtotal = $331,100 )
2023	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Child Health and Human Development Extramural Research	000	2	3/15/2023	NON-COMPETING CONTINUATION	$331,100
														Subtotal = $331,100

Issue Date FY: 2022 ( Subtotal = $331,100 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Child Health and Human Development Extramural Research	000	1	7/4/2022	NEW	$331,100
														Subtotal = $331,100

Grand Total All Awards = $1,652,189

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Regulation and function of H2A.Z during the mid-blastula transition

Award Number: R01HD105489

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/04/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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