Tuesday, July 1, 2025 7/1/2025

Deciphering the molecular mechanisms of histone code recognition by ATAD2/B

Award Number: R01GM129338
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2023

Group Awards By:

View Award Description

Deciphering the molecular mechanisms of histone code recognition by ATAD2/B - ATAD2 is an important co-activator of the estrogen and androgen receptors. ATAD2 is known to be up- regulated in multiple different types of cancer including breast, lung, gastric, endometrial, renal, and prostate. Up-regulation of ATAD2 is often correlated with poor patient outcomes, and can be used as prognostic marker. Furthermore, silencing the expression of ATAD2 through RNA interference inhibits cell proliferation and promotes apoptosis in ovarian carcinoma, and inhibits migration and invasion of hepatocellular carcinoma and colorectal cancer cells. ATAD2B, is a poorly studied paralog of the ATAD2 gene, and although ATAD2 and ATAD2B are highly conserved, there is little known about the function of ATAD2B or its role in oncogenesis. Both the ATAD2/B proteins contain two conserved domains: an AAA ATPase domain and a bromodomain. The overall objective of the proposed research is to determine how di-acetyllysine recognition by the ATAD2/B bromodomains regulates the cellular function of these proteins. This proposal aims to: (1) characterize how cross-talk between histone modifications modulate acetyllysine recognition by the ATAD2/B bromodomains; (2) outline the molecular mechanism(s) of di-acetylated histone recognition by the ATAD2/B bromodomains; (3) determine the functional significance of di-acetyllysine recognition by the ATAD2/B bromodomains. A unique combination of in vitro biochemical, biophysical, and structural biology studies on the ATAD2/B bromodomains will be coupled with in vivo functional genomic investigations using a breast cancer progression model to characterize the biological roles of the ATAD2/B bromodomains. We will evaluate the impact of neighboring histone modifications on histone H4 tail recognition using peptide array assays in combination with isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) chemical shift perturbation techniques. We will determine the structural features of ATAD2/B bromodomains required for recognition of di-acetylated histone tail ligands using NMR and/or X-ray crystallography. To characterize the binding mode of the ATAD2/B bromodomains with their histone ligands we will carry out analytical ultracentrifugation, size-exclusion chromatography, ITC, and NMR T1/T2 relaxation experiments. Site-directed mutagenesis coupled with NMR and ITC will be used to measure the effects on ligand binding, and identify differences in the binding pockets of the ATAD2/B bromodomains. We will compare the genome-wide associations of ATAD2/B with histone H4 acetylation patterns in a breast cancer progression model to determine the impact of ATAD2/B on breast cancer cell phenotypes using ChIP-seq and RNA-seq, followed by cellular migration and invasion assays. Our multi-faceted approach will correlate specific histone modifications with ATAD2/B binding and action, which will allow us to connect histone H4 acetylation marks to bromodomain function in cancer cell proliferation. Overall, our integrated biochemical, biophysical, structural biology and functional genomics approach will reveal the biological roles of ATAD2/B and facilitate the discovery of novel drug targets to help overcome 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: 2024 ( Subtotal = -$3,383 )
2024	2022	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Biomedical Research and Research Training	000	4	1/11/2024	SUPPLEMENT FOR EXPANSION	-$3,383
														Subtotal = -$3,383

Issue Date FY: 2022 ( Subtotal = $10,140 )
2022	2022	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Biomedical Research and Research Training	000	4	5/31/2022	SUPPLEMENT FOR EXPANSION	$10,140
2022	2021	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Biomedical Research and Research Training	001	4	6/17/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $10,140

Issue Date FY: 2021 ( Subtotal = $643,290 )
2021	2021	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Biomedical Research and Research Training	002	4	8/26/2021	SUPPLEMENT FOR EXPANSION	$90,838
2021	2021	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Biomedical Research and Research Training	001	4	8/19/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$552,452
2021	2021	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Biomedical Research and Research Training	004	4	9/5/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$419,319
2021	2020	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	3	8/18/2021	NON-COMPETING CONTINUATION	$0
2021	2020	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	003	3	9/5/2021	NON-COMPETING CONTINUATION	-$419,319
														Subtotal = $643,290

Issue Date FY: 2020 ( Subtotal = $481,491 )
2020	2020	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	3	8/28/2020	NON-COMPETING CONTINUATION	$481,491
														Subtotal = $481,491

Issue Date FY: 2019 ( Subtotal = $478,681 )
2019	2019	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	2	8/30/2019	NON-COMPETING CONTINUATION	$478,681
														Subtotal = $478,681

Issue Date FY: 2018 ( Subtotal = $454,712 )
2018	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	1	9/19/2018	NEW	$454,712
														Subtotal = $454,712

Grand Total All Awards = $2,064,931

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Deciphering the molecular mechanisms of histone code recognition by ATAD2/B

Award Number: R01GM129338

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/19/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer