# Epigenetic regulation of erythropoiesis > **NIH NIH R56** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $417,000 ## 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 have showed the GATA-1 can interact with HDAC1 containing NuRD corepressor complex in FOG-1 dependent manner for GATA-1 mediated gene activation and repression. We have also established that GATA-1 can interact with HDAC1 through a FOG-1 independent manner. This interaction is essential for GATA-1 deacetylation and erythrocyte differentiation in vitro, and erythrocyte and megakaryocyte differentiation in mice. The repression function through this interaction can be two folds, it may through constitutive acetylation of GATA-1 and it may also through loss of HDAC1 interacting proteins. We have performed proteomic analysis and found that GATA-1 interacts with BCL11A through HDAC1 dependent manner. Therefore, we hypothesize that HDAC1 regulates GATA-1 activity through deacetylation and interacting with key regulators that mediates erythroid differentiation and globin gene expression. In this proposal, we will first investigate the role of GATA-1 acetylation in GATA-1 mediated gene transcription program and global GATA-1 recruitment and chromatin accessibility. We have identified key interacting proteins with acetyl-mimicking and non-acetyl-mimicking proteins through LC-MS/MS. We will perform in-depth studies on differential recruitment of other GATA-1 interacting proteins that potentially alter GATA-1 binding landscape and target gene expression in vitro and in a mouse model. We will also study the importance of HDAC1 mediated GATA-1 and BCL11A interaction in fetal globin gene expression and erythroid differentiation. Preliminary Cut and run study showed that the BCL11A KD or mutation reduces GATA-1 recruitment at fetal globin locus but not at adult globin locus, suggesting negative role of GATA-1 in fetal globin gene expression. This claim is further supported by significantly upregulation of fetal globin gene expression in Mx1 cre GATA- 1cKO mice. We therefore will study the mechanism of how GATA-1 negatively regulates fetal globin gene expression. We will study how BCL11A regulates GATA-1 recruitment and activity in fetal globin gene expression and how GATA-1 collaborate with BCL11A for -globin gene repression. The role of GATA- 1/BCL11A interaction in globin gene promoter/enhancer interaction and global genome organization will also be study to have a comprehensive view of the role of GATA-1 in regulating erythrocyte function through interacting with BCL11A. Thus, this study will lead to novel in depth understanding of GATA-1 function in erythropoiesis and beyond. ## Key facts - **NIH application ID:** 11192954 - **Project number:** 2R56HL144712-05 - **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR - **Principal Investigator:** Yi Qiu - **Activity code:** R56 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $417,000 - **Award type:** 2 - **Project period:** 2019-01-15 → 2026-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11192954 ## Citation > US National Institutes of Health, RePORTER application 11192954, Epigenetic regulation of erythropoiesis (2R56HL144712-05). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11192954. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*