# Understanding how two related mammalian histone acetyl transferase co-activators, SAGA and ATAC, differentially regulate chromatin dynamics and transcription

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $348,682

## Abstract

UNDERSTANDING HOW TWO RELATED HISTONE ACETYL TRANSFERASE CO-ACTIVATORS, SAGA
 AND ATAC, DIFFERENTIALLY REGULATE CHROMATIN DYNAMICS AND TRANSCRIPTION
PROJECT SUMMARY
Histone post translational modifications (PTMs) and the complexes that install them and read them, control
many aspects of eukaryotic genome function including transcription, DNA repair and replication. As a result of
histone PTM writer’s broad functions, they are essential in organismal development, aging and numerous
diseases including cancer, heart disease, and even HIV integration. The majority of histone writers target the
disordered N-terminal tail regions. Numerous histone writers have been identified and studied genetically,
biochemically and structurally. Surprisingly, mechanistic studies are primarily limited to interactions between
histone tail peptides and catalytic subunits, resulting in key gaps in understanding how histone readers/writers
within their full native complexes interact and regulate chromatin structure, dynamics, accessibility and
transcription. Recently, we developed the methods to purify biochemical quantities of endogenous human
SAGA and ATAC complexes, which are related, but functionally distinct essential transcription co-activators.
This allows us to quantitatively investigate how these two large multi-subunit complexes function relative to
their common catalytic subunit, KAT2A, alone. Leveraging this, we recently found that
(i) The endogenous SAGA and ATAC complexes acetylate histone octamers much more efficiently than the
KAT2A acetyltransferase alone. (ii) The acetylation efficiency of endogenous SAGA and ATAC complexes are
dramatically inhibited by unmodified nucleosomes relative to unmodified histone octamer. (iii) The SAGA and
ATAC HAT modules acetylate histone H3K9 similarly relative to KAT2A alone, but the SAGA HAT module
acetylates H3K9 in unmodified nucleosomes much more efficiently than the ATAC HAT complex or KAT2A
alone. (iv) In mouse ES cells, deletion of the SAGA HAT module does not strongly affect global H3K9
acetylation, while deletion of the ATAC HAT module results in a significant reduction in overall H3K9
acetylation.
These findings have led us to investigate the hypothesis that histone PTM readers/writers target chromatin
properties through their accessory proteins to dynamically influence chromatin dynamics and accessibility.
(1) Determine the chromatin properties that regulate reading and writing by the mammalian HAT complex
SAGA.
(2) Elucidate how the different subunits of the related mammalian HAT complexes, SAGA and ATAC,
differentially control their targeting and chromatin modifying activity.
(3) Determine the functional differences between SAGA and ATAC in mouse embryonic stem cells and during
their differentiation.
Together these aims provide a mechanistic and functional foundation for understanding of how two key
transcriptional co-activators, SAGA and ATAC, differentially regulate chromatin dynamic and transcription.

## Key facts

- **NIH application ID:** 9859420
- **Project number:** 5R01GM131626-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Michael Guy Poirier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,682
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859420

## Citation

> US National Institutes of Health, RePORTER application 9859420, Understanding how two related mammalian histone acetyl transferase co-activators, SAGA and ATAC, differentially regulate chromatin dynamics and transcription (5R01GM131626-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859420. Licensed CC0.

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