Yi Qiu, Ph.D.
Office: CGRC 356
Phone: (352) 273-8201
Education and Training
Ph.D. – Mississippi State University (Animal Physiology)
M.Sc. – Chinese Academy of Science in Shanghai, China (Entomology)
B.Sc. – Peking University, China (Zoology)
Postdoc Fellow – Roland Stein, Vanderbilt University
Research Fellow – Gordon Hager, NCI/NIH
My research interests have been focused on function and regulation of histone deacetylases in development and cancer. We are the first group demonstrated that histone deacetylase 1 (HDAC1) can be acetylated by p300. Acetylation attenuates the deacetylase activity of HDAC1. Further we show that acetylated HDAC1 also trans-represses the activity of HDAC2, a deacetylase that is often coexist with HDAC1 in a corepressor complex. Therefore, our study unveiled a new mechanism of collaborative regulation by HDAC1/2 containing coregulator complexes. We research also shows that in contrast to general view of that p300 and HDACs are recruited to chromatin through interaction with chromatin binding proteins, p300 and HDAC1 can be directly recruited to chromatin through direct interaction with DNA and histones. Importantly, p300 and HDAC1 compete for chromatin binding. Therefore, our result support the hypothesis that p300 and HDAC1 is constantly cycled on active chromatin. Our recent study focused on role of HDAC1 in modulation of TFIID complex activity in gene transcription and ES cell development.
Another aspect of our research is to study the role of histone deacetylases in hematopoiesis. Our study shows that histone deacetylase 1 (HDAC1) is a master regulator for erythropoiesis as it counter regulates GATA-1 and PU.1 activity. We found that GATA-1 and HDAC1 direct interaction mediates deacetylation of GATA-1 and global recruitment of GATA-1. We have created GATA-1 knock in mice with HDAC1 binding site mutated. The mice is defective in GATA-1 mediated hematopoiesis. Therefore, the study demonstrate the key role of HDAC1 in regulation GATA-1 activity.
Histone deacetylase inhibitor (HDACi) is emerging as a new class of anticancer agents as well as potential drug for reactivation of fetal globin in adult erythroid cells. However, the adverse effect of HDACi is not evaluated. Therefore we are interested in studying the impact of HDACi in hematopoietic stem cell self-renewal and differentiation potential. We also have our research aimed to understand how HDAC1 and other epigenetic factors regulate cancer cell survival and chemoresistance. We show that the overexpression of HDACs, p300 and hSET1 in cancer cells directly promote colon cancer cell survival. The transcription of HDAC1 is regulated by interplay of transcription factors Sp1/Sp3 and these epigenetic modulators. The acetylation of HDAC1 also plays an important role in regulating DNA repair and p53 mediated stress response. Currently we are investigating the role of class I deacetylases in promoting cancer stem cell survival and chemoresistance in acute myeloid leukemia (AML) and colon cancer model. We found the inhibition of class I histone deacetylases specifically targets the population of cells that are positive for stem cell markers and resensitizes cancer cells to chemotherapy. Therefore, histone deacetylase inhibitors are potential chemotherapeutic drugs for chemoresistant cancer treatment.
Li X, Mei Y, Yan B, Vitriol E, Huang S, Ji P and Qiu Y. Histone deacetylase 6 regulates cytokinesis and erythrocyte enucleation through deacetylation of formin protein mDia2. Haematologica 102(6):984-994 (2017) | PubMed
Luo H, Shenoy AK, Li X, Jin Y, Jin L, Cai Q, Tang M, Reisman D, Wu L, Qiu Y, Dou Y, Casero RA and Lu J. MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition. Cell Rep 15(12):2665-78 (2016) | PubMed
Li Y, Schulz VP, Deng C, Li G, Shen Y, Tusi BK, Ma G, Stees J, Qiu Y, Steiner LA, Zhou L, Zhao K, Bungert J, Gallagher PG and Huang S. Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. Nucleic Acids Res. 44(15):7173-88 (2016) | PubMed
Deng C, Li Y, Zhou L, Cho J, Patel B, Terada N, Li Y, Bungert J, Qiu Y* and Suming Huang*. HoxBlinc RNA recruits Set1/MLL complexes to activate Hox gene expression patterns and mesoderm lineage development. Cell Rep. 14(1):103-14 (2016) | PubMed *co-coresponding authors
Yang H, Yan B, Liao D, Huang S and Qiu Y. Acetylation of HDAC1 and degradation of SIRT1 form a positive feedback loop to regulate p53 acetylation during heat shock stress. Cell Death & Dis. 6:e1747. (2015) | PubMed
Tusi BK, Deng C, Salz T, Zeumer L, Li Y, So ECW, Morel LM, Qiu Y* and Huang S*. Setd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement. FASEB J 29(4):1505-15 (2015) | PubMed *co-corresponding authors
Yang H, Salz T, Zajac-Kaye M, Liao D, Huang S and Qiu Y. The overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. FASEB J 28(10):4265-79 (2014) | PubMed
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Major Teaching Responsibilities
GMS 6692 Research Conference in Anatomy and Cell Biology
GMS 6421 Advanced Cell Biology
GMS 6062 Protein Trafficking
GMS 6647 Transcription Regulation
GMS 6644 Apoptosis
GMS 6061 The Nucleus