IQB Handbook
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19ACHIEVEMENTPUBLICATIONKimura A, Umehara T, Horikoshi M. Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing. Nat Genet. 2002 Nov;32(3):370-7. DOI:10.1038/ng993Natsume R, Eitoku M, Akai Y, Sano N, Horikoshi M, Senda T. Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Nature. 2007 Mar 15;446(7133):338-41. DOI:10.1038/nature05613Akai Y, Adachi N, Hayashi Y, Eitoku M, Sano N, Natsume R, Kudo N, Tanokura M, Senda T, Horikoshi M. Structure of the histone chaperone CIA/ASF1-double bromodomain complex linking histone modifications and site-specific histone eviction. Proc Natl Acad Sci U S A. 2010 May 4;107(18):8153-8. DOI:10.1073/pnas.0912509107HORIKOSHIMASAMIPH.D. (1985) THE UNIVERSITY OF TOKYOASSISTANT PROFESSOR (1989) THE ROCKEFELLER UNIVERSITYASSOCIATE PROFESSOR (1992) INSTITUTE OF APPLIED MICROBIOLOGY, THE UNIVERSITY OF TOKYOASSOCIATE PROFESSOR (2007) INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYOASSOCIATE PROFESSOR(2018) IQB / INSTITUTE FOR QUANTITATIVE BIOSCIENCES, THE UNIVERSITY OF TOKYO●MEMBER■ ASSOCIATE PROFESSOR :HORIKOSHI MASAMI■ ASSISTANT CLERK :HASEGAWA KYOKOPUBLICATIONPUBLICATIONhe fate of a cell is determined by gene expression. After the general principals of the maintenance and conversion of genetic information such as the double helical structure of DNA (Nature, 1953), the operon theory (J.Mol.Biol., 1961) and the genetic code (Proc.Natl.Acad.S-ci.U.S.A., 1961) were presented, the detailed studies of individual research fields became the mainstream of biology. Can we expect the discovery of a new general principle on biologi-cal phenomena? Horikoshi was engaged in the study of eukaryotic transcriptional regulation and accumulated invaluable experiences in which he was one of the leading figures in the relevant fields. Then, his study focused on chromatin, which was one of the uncharted research areas. Because a nucleosome is the basic unit of eukaryotic chromosome structure, histones must have changed the frameworks of gene regulation. Utilizing a TFIID domain, which was functionally unknown and had histone fold structure, Horikoshi obtained a number of novel factors that would be a part of a new framework of gene regulation and succeeded in identifying their functions. Investigating those factors, he proposed novel models as follows. “Negotiable border model” shows how boundaries between euchromatic and heterochromatic regions are established (Nature Genet., 2002). “Yawara split model” shows that a factor that we named as CIA has a histone H3-H4 tetramer-disrupting activity (Nature, 2007). “Hi-MOST model” shows how transcription is activated through confor mational change of nucleosome with histone modification (Proc.Natl.Acad.Sci.U.S.A., 2010).Horikoshi's next strategy was the functional analyses by point mutagenesis of exposed and buried amino acid residues in histones (Genes Cells, 2007; 2009). These GLASP and GLAMP analyses provided results that indicated that modified residues on histone tails would not affect cell proliferation. They were in conflict with “Histone code hypothesis”. Horikoshi proposed a novel “Modification web theory” presenting that histone modification network system has a robust structure against distur-bance. “Signal router theory” was also proposed. It suggests that unstructured regions of histone tails receive, process and convey the informa-tion, and contribute to the formation, growth and evolution of “Modification web”. This uncovers the possible physiological significance of intrinsically disordered region (IDR) of proteins (Genes Cells, 2009). About half part of the structure of any eukaryotic protein consists of IDR.Horikoshi's recent studies gave answers to the questions unsolved for five to ten decades, such as “how the roles of a common subunit in one multisubunit protein complex are distinguished from its roles in other complexes” (Proc.Natl.Acad.Sci.U.S.A., 2014) and “how the mechanism of evolutionarily early transcription systems billions of years ago is uncovered without DNA of ancient organisms” (Sci.Rep., 2016; Cell Rep., 2017).TProposed principles in gene regulation and our contributions

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