Basic Medicine, Molecular and Cellular Biology, Genomics, Genetics and Epigenetics
We Try to Understand Disease Processes through Exploration of the Regulatory Mechanisms of Gene Expression and Epigenome
Medical Sciences Course
- Master / Doctoral Degree
- IGARASHI, Kazuhiko
Professor, M.D. Ph.D.
igarashi*med.tohoku.ac.jp (Please convert "*" into "@".)
- Regulation of the development and differentiation of immune cells by transcription factors and epigenome, and its pathological implications
- Regulation of erythropoiesis and immune cells by the prosthetic group heme, and its pathological implications
- Nuclear proteins network for histone methylation, and its pathological implications
transcription factors, chromatin, epigenome, B lymphoid cell, macrophage, erythroid cell,
mass spectrometry analysis, next generation sequencing, bioinformatics, mouse, molecular biology
Cell differentiation is dependent on transcription factors and epigenetic modifications of chromatin that together regulate lineage- and stage-specific gene expression. Using immune cells as a model, we are trying to understand their differentiation based on transcription factors. Our recent major findings include 1) regulation of antibody class switching, somatic hypermutation, and plasma cell differentiation by a gene regulatory network (GRN) involving the transcription repressor Bach2, 2) regulation of the bifurcation of B and myeloid cells by Bach2 and Bach1 in the common lymphoid progenitor cells, and 3) regulation of tissue specific macrophages such as alveolar macrophages by Bach2 and its implication in the pathology of alveolar proteinosis. We are currently trying to extend these findings to the field of tumor immunity. Since we have also found that heme regulates both Bach1 and Bach2, the role of heme as a signaling molecule in the immune system is another focus of the laboratory.
Another line of the research is the regulation of methylation of histone and DNA by the transcription factors. We found that methionine adenosyltransferase II (MATII) is present in the nuclei and interacts with transcription factors. This enzyme synthesizes S-adenosylmethionine (SAM) which provides the methyl group for the transmethylation reactions. We are trying to understand how the nuclear and chromatin localizations of MATII regulate histone methylation and chromatin function.
Figure 1. Gene regulatory network for B cell differentiation and responses
Figure 2. Heme as a signaling molecule in the immune system
- Tanaka, H. et al. Epigenetic regulation of the Blimp-1 gene in B cells involves Bach2 and histone deacetylase 3. J. Biol. Chem. 291, 6316-6330 (2016)
- Igarashi, K. et al. Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network. Immunol. Rev. 261, 116-125 (2014)
- Itoh-Nakadai, A. et al. The transcription repressors Bach2 and Bach1 promote B cell development by repressing myeloid program. Nature Immunol. 15, 1171-1180 (2014).
- Nakamura, A. et al. The transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. J. Exp. Med. 210, 2191-2204 (2013).
- Watanabe-Matsui, M. et al. Heme regulates B cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2. Blood 117, 5438-5448 (2011).
- Katoh, Y. et al. Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol. Cell 41, 554-566 (2011).