Novel epigenetic regulation of the gene expression program by chromosome dynamics

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390068
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Shiga University of Medical Science (2013); Kyoto University (2011-2012)
• Principal Investigator: AGATA YASUTOSHI 滋賀医科大学, 医学部, 教授 (60263141)
• Co-Investigator(Renkei-kenkyūsha): IKAWA Tomokatsu 理化学研究所 統合生命医科学研究センター, 免疫細胞再生研究YCIラボ, 研究員 (60450392) ; SATOH Fumiaki 京都大学, 医学研究科, 准教授 (20467426)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 染色体ダイナミクス / エピジェネティクス / コヒーシン / Rad21 / CTCF / E2A / ChIP-Seq / 染色体構造変化

Outline of Final Research Achievements

Cohesin essential for chromosome cohesion and the insulator component CTCF regulate the expression of genes, which are critical for cell differentiation, by chromosome dynamics. To identify genes that are regulated by these proteins and also critical for T cell differentiation, we performed ChIP-Seq analyses using the EBF-KO progenitor cell line, which differentiates to T cells upon Notch stimulation, and found that the cohesin subunit Rad21 and CTCF bound to the genes such as Tcf7 and Bcl11b, master regulators of T cell differentiation. We thus depleted Rad21 and CTCF by knockdown and found that Tcf7 and Bcl11b expression was further increased and T cell differentiation was facilitated. In contrast, when we depleted E2A essential for TCRβ locus contraction, Bcl11b and Notch target genes were downregulated and T cell differentiation was abrogated. These results suggest that Rad21/CTCF and E2A regulate T cell differentiation in a negative or positive manner, respectively.

Free Research Field

分子生物学、免疫学