Tuesday, April 16, 2024 4/16/2024

Elucidating how pioneer factors drive dynamic chromatin accessibility during zygotic genome activation

Award Number: F31HD104443
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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PROJECT SUMMARY Dynamic remodeling of the three-dimensional organization of the genome regulates gene expression to coordinate the healthy development of organisms and can impact disease progression when dysregulated. Recent advances have enabled the visualization of accessible chromatin in situ in fixed samples; however, we still do not fully understand how changes in chromatin organization occur in vivo during vertebrate development, especially at the single-cell level. Therefore, the goal of this project is to study the dynamic remodeling of chromatin organization during zygotic genome activation, when the transcriptionally silent embryo first initiates transcription of its own genes and genome architecture is dramatically remodeled. First (Aim 1), I will investigate the dynamic spatial organization of chromatin accessibility during genome activation in zebrafish. To do so, I will use Live-ATAC, a method I recently developed. Live-ATAC enables real time detection of chromatin accessibility in vivo at the single-cell level in living embryos. Using this method, I will determine precisely when and where chromatin accessibility is gained as the embryo undergoes genome activation and transcription is initiated. Second (Aim 2), I will use Live-ATAC in mutant embryos to dissect the role of pioneer transcription factors in dynamically remodeling chromatin accessibility during genome activation. Specifically, I will use embryos lacking functional Nanog, Oct4, and Sox19b which are maternally supplied transcription factors have been implicated in pluripotency and genome activation. Simultaneously, I will measure transcription of the first zygotically transcribed genes to determine the causal relationships between transcription factors, chromatin accessibility, and transcription in real time in vivo. Altogether, this work will provide an unprecedented view of how chromatin organization is dynamically remodeled during cellular reprogramming and begin elucidating the underlying mechanisms. This will inform our understanding of how three-dimensional genome organization may affect human embryogenesis and disease given the likely conserved regulatory principles.


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: 2024 ( Subtotal = $32,654 )
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	000	4	10/24/2023	NON-COMPETING CONTINUATION	$32,654
														Subtotal = $32,654

Issue Date FY: 2023 ( Subtotal = $32,594 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	001	3	2/10/2023	NON-COMPETING CONTINUATION	$942
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	000	3	11/7/2022	NON-COMPETING CONTINUATION	$31,652
														Subtotal = $32,594

Issue Date FY: 2022 ( Subtotal = $43,352 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	001	2	4/27/2022	NON-COMPETING CONTINUATION	$717
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	002	2	5/27/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	000	2	11/4/2021	NON-COMPETING CONTINUATION	$42,636
														Subtotal = $43,352

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	001	1	11/4/2020	NEW	$0
2021	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	000	1	11/4/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $42,120 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Child Health and Human Development Extramural Research	000	1	9/24/2020	NEW	$42,120
														Subtotal = $42,120

Grand Total All Awards = $150,720

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Elucidating how pioneer factors drive dynamic chromatin accessibility during zygotic genome activation

Award Number: F31HD104443

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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