# Epigenetic regulation of hematopoiesis

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $395,800

## Abstract

Project Summary/Abstract
 Histone deacetylases (HDACs) are a group of epigenetic enzymes that are important in
regulating gene transcription and other cellular processes. HDAC1 is implicated in various
developmental program, including hematopoiesis. We and others previously showed that
HDAC1 is an important regulator for GATA-1 function in FOG-1 dependent manner. During
erythroid differentiation, HDAC1 within FOG-1 associated NuRD complex is acetylated and
becomes inactive. Inactivated HDAC1 converts the NuRD into a coactivator complex to activate
GATA-1 dependent gene transcription. Here we show that GATA-1 can also associate with
HDAC1 in a FOG-1 independent manner, importantly, this association is required for GATA-1
deacetylation, therefore suggesting another layer of regulation for GATA-1 function. The
significance of these findings is demonstrated by our observation that mutations in GATA-1 that
disrupt HDAC1 interactions (GATA-1 2RA mutants) cause erythroid differentiation defects in
mice. The central hypothesis for this proposal is that GATA-1 and HDAC1 interaction as
well as acetylation of GATA-1 regulates the erythroid differentiation program and
erythroid enhancer/promoter chromatin structure during erythropoiesis. In this proposal,
we will investigate the mechanism underlying the regulation of GATA-1 activity by HDAC1 in a
FOG-1 independent manner and to study the importance of direct HDAC1 binding in GATA-1
mediated gene transcription program and global GATA-1 recruitment and chromatin
accessibility. Finally we propose to study the role of HDAC1 in regulating erythroid lineage
differentiation by direct interacting with GATA-1 in a mouse model. By completion of this
proposal, we will be able to gain insight into the function of dynamic GATA-1
acetylation/deacetylation and the importance of GATA-1/HDAC1 direct interactions. We will
also learn the differential requirement of FOG-1 dependent and independent HDAC1
recruitment for erythropoiesis. The Knock in mouse work will further enable us to delineate the
requirement of GATA-1/HDAC1 interactions for lineage specific development. Thus, this study
will lead to in depth understanding of GATA-1 function in erythropoiesis and beyond.

## Key facts

- **NIH application ID:** 10131913
- **Project number:** 7R01HL144712-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Yi Qiu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,800
- **Award type:** 7
- **Project period:** 2019-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131913

## Citation

> US National Institutes of Health, RePORTER application 10131913, Epigenetic regulation of hematopoiesis (7R01HL144712-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10131913. Licensed CC0.

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