RIKEN IMS Annual Report 2023
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In higher eukaryotes, including humans, only a small portion of the genome 24EnvironmentalstimuliActive transcriptionTEs influence host transcription regulationTransposon coding lociRepressive transcriptionNucleusencodes proteins, with most of it comprising non-genic elements such as transposons, endogenous viruses, and functional RNA/DNA sequences. Mobile non-genic elements, specifically, pose potential threats due to their repetitive nature, transposability, and transcriptional activity, leading to genome instabil-ity and chromosome damage. Organisms employ various mechanisms, includ-ing functional non-coding RNAs, to rigorously control the instability of non-genic elements. The antagonism between mobile non-genic elements and their regulatory mechanisms may dynamically influence genome structure and chro-matin state, impacting gene function and contributing to phenotypic diversifi-cation and adaptive responses to environmental stress. Our study aims to validate the hypothesis that the conflict between the expression of mobile non-genic elements and their repressive mechanisms provides the genome with the flexibility to respond to different environmental stimuli (Figure). We are investigating fluctuations in transposons and their re-pression mechanisms in response to various environmental changes, including internal factors such as development, and external stressors like viral infection and temperature. To understand the molecular mechanism of transposon regu-lation machinery, we have developed a cell line-based reconstruction system and we plan to combine this with in vivo analysis to understand the potential impact on phenotypes. Our systematic investigation will explore the response of transposons and their regulatory mechanisms to environmental stimuli, ex-amine the effects on chromatin state and gene expression, and assess their phe-notypic consequences. By deciphering the intricate interplay between mobile non-genic elements and their regulatory networks, we aim to shed light on the mechanisms underlying genome plasticity and its role in facilitating adaptive responses to varying environmental conditions.Figure: Genomic plasticity is shaped by the an-tagonism between transposons and their regu-latory mechanismsThe activation of mobile non-genic elements, such as transposons (TE), is observed in response to various environmental stimuli. Additionally, these activations can induce the regulatory functions of various transpo-son regulation machineries, such as small RNA silencing, the HUSH complex, and KRAB-ZFP. Together with acti-vated mobile non-genic elements, they may contribute to genome plasticity by inducing changes in genome structure, gene expression, and epigenome patterns.Recent Major PublicationsYamamoto-Hino M, Ariura M, Tanaka M, Iwasaki YW, Kawaguchi K, Shimamoto Y, Goto S. PIGB maintains nuclear lamina organization in skeletal muscle of Drosophila. J Cell Biol 223, e202301062 (2024)Iwasaki YW, Koseki H, Ito S. In preprints: revisiting RNA in PRC2. Development 150, dev202440 (2023)Takeuchi C, Yokoshi M, Kondo S, Shibuya A, Saito K, Fukaya T, Siomi H, Iwasaki YW. Mod (mdg4) variants repress telomeric retrotransposon HeT-A by blocking subtelomeric enhancers. Nucleic Acids Research 50, 11580-11599 (2022)Invited presentationsIwasaki YW. “Regulatory mechanism of transposable elements” OIST-JST Joint Meeting (Onna-son, Japan) January 2024Iwasaki YW. “Genomic plasticity shaped by the an-tagonism between transposons and their regulatory mechanisms” The 97th Annual Meeting of the Japanese Pharmacological Society (Kobe, Japan) December 2023Iwasaki YW. “Transcriptional regulation of telomeric transposon via enhancer architecture” The 47th Annual Meeting of the Molecular Biology Society of Japan (Kobe, Japan) December 2023Iwasaki YW. “Decoding the Non-coding Genome” 1st OIST-RIKEN meeting (Onna-son, Japan) November 2023Iwasaki YW. “Co-transcriptional silencing by nuclear PIWI-piRNA complex” The 3rd Asia RNA Club (Online) September 2023chromatin conformational change epigenetic regulationOFFTransposon regulatorymachineriesgene expression regulationONLaboratory for Functional Non-coding GenomicsTeam Leader: Yuka W. Iwasaki

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