Comprehensive analysis of gene expression regulation during mononuclear phagocyte development

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04860
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Yokohama City University
• Principal Investigator: Tamura Tomohiko 横浜市立大学, 医学研究科, 教授 (50285144)
• Co-Investigator(Kenkyū-buntansha): 中林 潤 横浜市立大学, 先端医科学研究センター, 准教授 (80322733)
• Co-Investigator(Renkei-kenkyūsha): KUROTAKI Daisuke 横浜市立大学, 医学部, 講師 (10568455) ; NISHIYAMA Akira 横浜市立大学, 医学部, 准教授 (80589664)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: エンハンサー / 単球 / 樹状細胞 / 転写因子 / ChIP-seq

Outline of Final Research Achievements

Monocytes and dendritic cells (DCs), called mononuclear phagocytes, are critical for host defense and tissue homeostasis. These cells develop from bone marrow hematopoietic stem cells via intermediate progenitors. However, molecular mechanisms underlying the regulation of gene expression during monocyte and DC development still remain obscure. In this research project, we analyzed the genome-wide dynamics of enhancer landscape, gene expression, and chromatin binding of key transcription factors in various differentiation stages of myeloid cells. We found that the chromatin binding of IRF8, which recruits binding of PU.1, induces the formation of monocyte and DC-specific enhancers in the progenitor stages, leading to the future expression of genes that confer the characteristics of mononuclear phagocytes. These results contribute to a comprehensive understanding of how transcription factors affect chromatin to regulate gene expression during cell differentiation.

Free Research Field

血液学