Friday, December 12, 2025 12/12/2025

A New Histone H3 Modification Regulates Epigenetic Programming and Gene Expression in Breast Cancer

Award Number: R01CA274924
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/08/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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A New Histone H3 Modification Regulates Epigenetic Programming and Gene Expression in Breast Cancer - Project Summary Distinct histone modifications, on N or C-terminal tails, act as a “histone code” to elicit downstream events. Histone subunit post-translational modification (PTM), such as methylation, acetylation and phosphorylation regulates epigenetic regulation and gene expression in diseases such as cancer. Here we identified a new PTM on H3 called hydroxylation on proline 16, which is catalyzed by proline hydroxylase EglN2. Our preliminary data show that EglN2-mediated H3 Pro16-OH leads to increased Lysine (K)-Specific Demethylase 5A (KDM5A) binding corresponding with decreased H3K4me3 in breast cancer. We hypothesize that H3 prolyl hydroxylation mediated by EglN2 recruits KDM5A therefore controlling gene expression important in breast cancer. This is the first study reporting H3 Prolyl hydroxylation and its potential role in epigenetic regulation and gene expression in cancer. In Specific Aim 1, we will determine the effet of H3 prolyl hydroxylation on epigenetic regulation and gene expression on a genome wide scale in breast cancer cells. In Specific Aim 2, we will elucidate the molecular mechanism by which H3 prolyl hydroxylation regulates epigenetic reprogramming by recruiting KDM5A. In Specific Aim 3, we will elucidate the molecular mechanism by which H3 prolyl hydroxylation regulates Wnt/b-Catenin signaling in breast cancer cells. Successful completion of this proposal will characterize a new H3 post-translational modification in its epigenetic regulation and gene expression important in breast cancer.


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 = $384,949 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Cause and Prevention Research	000	4	12/5/2025	NON-COMPETING CONTINUATION	$384,949
														Subtotal = $384,949

Issue Date FY: 2025 ( Subtotal = $427,721 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Cause and Prevention Research	000	3	11/1/2024	NON-COMPETING CONTINUATION	$384,949
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Cause and Prevention Research	001	3	5/29/2025	NON-COMPETING CONTINUATION	$42,772
														Subtotal = $427,721

Issue Date FY: 2024 ( Subtotal = $406,336 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Cause and Prevention Research	001	2	4/16/2024	NON-COMPETING CONTINUATION	$21,387
2024	2024	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Cause and Prevention Research	000	2	11/2/2023	NON-COMPETING CONTINUATION	$384,949
														Subtotal = $406,336

Issue Date FY: 2023 ( Subtotal = $443,721 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Cause and Prevention Research	000	1	12/8/2022	NEW	$443,721
														Subtotal = $443,721

Grand Total All Awards = $1,662,727

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A New Histone H3 Modification Regulates Epigenetic Programming and Gene Expression in Breast Cancer

Award Number: R01CA274924

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/08/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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