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Targeting acetylated histone H4 by MLL4

Award Number: R01AG067664
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Targeting acetylated histone H4 by MLL4 - Project Summary Epigenetic mechanisms play a pivotal role in aging and are found disregulated in age-related disorders, including neurodegenerative diseases and cancer. The major indicator of alterations occurred in chromatin during aging is acetylation of lysine 16 of histone H4 (H4K16ac), a modification that is redistributed and raised in the healthy aged brain but is considerably lost in Alzheimer’s disease. On the molecular level, H4K16ac is involved in a wide array of fundamental cellular processes, including higher-order chromatin decompaction and folding, DNA damage repair, and gene expression. Despite the high importance of H4K16ac, very little is known about protein ligands that bind this mark. Our recent studies identified the plant homeodomain finger 6 of the histone methyltransferase MLL4 (MLL4PHD6) as a selective effector (or reader) of H4K16ac. The molecular mechanism underlying the recognition of H4K16ac by MLL4 is unknown and will be elucidated in the proposed studies. We hypothesize that the selective targeting of H4K16ac by MLL4 at specific genomic sites is necessary for transcriptional activation of MLL4 target genes and that this interaction provides a novel functional link between MLL4 that methylates lysine 4 of histone H3 (H3K4) and the acetyltransferase MOF that produces H4K16ac. We seek to define the molecular basis and functional significance of the previously uncharacterized crosstalk between vital histone marks. These studies are fundamental to our understanding of physiological activities associated with ‘writing and reading’ H4K16ac and are also essential to better understand the etiology of human age-related illnesses, including AD and other neurodegenerative disorders.


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 = $0 )
2026	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	000	4	1/30/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $516,989 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	000	4	3/7/2025	NON-COMPETING CONTINUATION	$474,786
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	001	4	6/9/2025	NON-COMPETING CONTINUATION	$42,203
														Subtotal = $516,989

Issue Date FY: 2024 ( Subtotal = $527,540 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	000	3	6/13/2024	NON-COMPETING CONTINUATION	$527,540
														Subtotal = $527,540

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	000	2	3/24/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $527,540 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	000	2	4/28/2022	NON-COMPETING CONTINUATION	$527,540
														Subtotal = $527,540

Issue Date FY: 2021 ( Subtotal = $527,540 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Aging Research	000	1	4/30/2021	NEW	$527,540
														Subtotal = $527,540

Grand Total All Awards = $2,099,609

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Targeting acetylated histone H4 by MLL4

Award Number: R01AG067664

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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