{"id":231,"date":"2022-08-23T10:29:21","date_gmt":"2022-08-23T01:29:21","guid":{"rendered":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/?page_id=231"},"modified":"2022-09-08T15:27:19","modified_gmt":"2022-09-08T06:27:19","slug":"english","status":"publish","type":"page","link":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/english\/","title":{"rendered":"Research"},"content":{"rendered":"\n

\u3000Cell type-dependent gene activation is enabled by the three-dimensional regulation of chromatin conformations, which involves “DNA-loop”. DNA-loop regulates transcriptional activation with the help of a multi-subunit co-activator called Mediator. Mediator directly connects activator which is bound to enhancer DNA with RNA polymerase II on the promoter DNA via a long DNA chain of several Kbps to Mbps, thereby forming the aforementioned DNA-loop structure in chromatin. A number of diseases have been linked to DNA-loop, including cancers, as DNA-loop plays a key role in forming clusters of enhancers, or super-enhancers, that drive unusually high level of expression of genes, such as oncogenes. Hence, DNA-loop may be a potential therapeutic target for selective disruption of oncogene expression. Notably, Mediator seems to have a key role in forming super-enhancer structure. Super-enhancers are clusters of DNA-loop, and they can drive high expression levels of oncogenes in cancer cells. Another interesting regulatory mechanism by Mediator is a formation of liquid-liquid phase separation (LLPS). LLPS represents a phenomenon in which proteins and\/or nucleic acids achieve higher local concentrations and form \u201cmembrane-less organelles\u201d.<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

\u3000Our laboratory aims to elucidate the atomic structure of DNA-loop using Cryo-electron microscopy and X-ray crystallography, to reveal the molecular mechanism of transcriptional initiation and epigenetic regulation thereof. So far, we established a protein co-expression system for the core Mediator of 15 subunits, which is the smallest functional unit of the Mediator, and performed X-ray crystallographic analysis. The result clarified that it is involved in the transcription initiation of Pol II on the promoter. We are also interested in chromatin structures constituting the DNA-loop. Applying cryo-electron microscopy analysis, we have recently characterized a unique chromatin structural unit H3-H4 octasome that resembles the normal nucleosome but lacks H2A and H2B.<\/p>\n\n\n\n

\"\"<\/figure>\n","protected":false},"excerpt":{"rendered":"

\u3000Cell type-dependent gene activation is enabled by the three-dimensional regulation of chromatin conformations…<\/p>\n","protected":false},"author":1,"featured_media":364,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"class_list":["post-231","page","type-page","status-publish","has-post-thumbnail","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/pages\/231","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/comments?post=231"}],"version-history":[{"count":4,"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/pages\/231\/revisions"}],"predecessor-version":[{"id":424,"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/pages\/231\/revisions\/424"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/media\/364"}],"wp:attachment":[{"href":"https:\/\/www.nozawa-lab.bio.titech.ac.jp\/wordpress\/wp-json\/wp\/v2\/media?parent=231"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}