# Targeting acetylated histone H4 by MLL4

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $527,540

## Abstract

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.

## Key facts

- **NIH application ID:** 10202000
- **Project number:** 1R01AG067664-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** TATIANA G KUTATELADZE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $527,540
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202000

## Citation

> US National Institutes of Health, RePORTER application 10202000, Targeting acetylated histone H4 by MLL4 (1R01AG067664-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10202000. Licensed CC0.

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