Details of the Researcher

PHOTO

Masaki Hosogane
Section
Graduate School of Medicine
Job title
Assistant Professor
Degree

  • 博士（医学）（東北大学）

  • 修士（医科学）（東北大学）

e-Rad No.
30734347

Research History 1

  • 2020/03 - Present
    Tohoku University　Assistant professor

Research Areas 1

  • Life sciences / Molecular biology /

Papers 9

  1. ALS-associated RNA binding proteins converge onUNC13Atranscription through regulation of REST

    Yasuaki Watanabe, Naoki Suzuki, Tadashi Nakagawa, Masaki Hosogane, Tetsuya Akiyama, Hitoshi Warita, Masashi Aoki, Keiko Nakayama

    2024/10/23

    DOI： 10.1101/2024.10.22.619761 　

  2. Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine. International-journal

    Daniel Arango, David Sturgill, Renbin Yang, Tapan Kanai, Paulina Bauer, Jyoti Roy, Ziqiu Wang, Masaki Hosogane, Sarah Schiffers, Shalini Oberdoerffer

    Molecular cell　82　(15)　2912-2912　2022/08/04

    DOI： 10.1016/j.molcel.2022.06.022 　

  3. SPT16 ubiquitylation by DCAF14-CRL4 regulates FACT binding to histones. International-journal

    Tadashi Nakagawa, Akane Morohoshi, Yuko Nagasawa, Makiko Nakagawa, Masaki Hosogane, Yasuhiro Noda, Toru Hosoi, Keiko Nakayama

    Cell reports　38　(12)　110541-110541　2022/03/22

    DOI： 10.1016/j.celrep.2022.110541 　

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    The histone chaperone complex FACT comprises SPT16 and SSRP1 and contributes to DNA replication, transcription, and repair, but how it plays such various roles is unclear. Here, we show that human SPT16 is ubiquitylated at lysine-674 (K674) by the DCAF14-CRL4 ubiquitin ligase. K674 is located in the middle domain of SPT16, and the corresponding residue of the yeast ortholog is critical for binding to histone H3.1-H4. We show that the middle domain of human SPT16 binds to histone H3.1-H4 and that this binding is inhibited by K674 ubiquitylation. Cells with heterozygous knockin of a K674R mutant of SPT16 manifest reduction of both SPT16 ubiquitylation and H3.1 in chromatin, a reduced population in mid S phase, impaired proliferation, and increased susceptibility to S phase stress. Our data thus indicate that SPT16 ubiquitylation by DCAF14-CRL4 regulates FACT binding to histones and may thereby control DNA replication-coupled histone incorporation into chromatin.

  4. Acetylation of Cytidine in mRNA Promotes Translation Efficiency Peer-reviewed

    Daniel Arango, David Sturgill, Najwa Alhusaini, Allissa A. Dillman, Thomas J. Sweet, Gavin Hanson, Masaki Hosogane, Wilson R. Sinclair, Kyster K. Nanan, Mariana D. Mandler, Stephen D. Fox, Thomas T. Zengeya, Thorkell Andresson, Jordan L. Meier, Jeffery Coller, Shalini Oberdoerffer

    Cell　175　(7)　1872-1886.e24　2018/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.cell.2018.10.030 　

    ISSN： 0092-8674

  5. Transforming growth factor β-induced proliferative arrest mediated by TRIM26- dependent TAF7 degradation and its antagonism by MYC Peer-reviewed

    Tadashi Nakagawa, Masaki Hosogane, Makiko Nakagawa, Akane Morohoshi, Ryo Funayama, Keiko Nakayama

    Molecular and Cellular Biology　38　(5)　pii: e00449-17　2018/03/01

    Publisher: American Society for Microbiology

    DOI： 10.1128/MCB.00449-17 　

    ISSN： 1098-5549 0270-7306

  6. Geminin is an indispensable inhibitor of Cdt1 in mouse embryonic stem cells Peer-reviewed

    Masaki Hosogane, Lena Bosu, Emiko Fukumoto, Hidetoshi Yamada, Soichiro Sato, Keiko Nakayama

    Genes to Cells　22　(4)　360-375　2017/04/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/gtc.12482 　

    ISSN： 1365-2443 1356-9597

  7. Lack of Transcription Triggers H3K27me3 Accumulation in the Gene Body Peer-reviewed

    Masaki Hosogane, Ryo Funayama, Matsuyuki Shirota, Keiko Nakayama

    Cell Reports　16　(3)　696-706　2016/07/19

    Publisher: Elsevier B.V.

    DOI： 10.1016/j.celrep.2016.06.034 　

    ISSN： 2211-1247

  8. Ras-Induced Changes in H3K27me3 Occur after Those in Transcriptional Activity Peer-reviewed

    Masaki Hosogane, Ryo Funayama, Yuichiro Nishida, Takeshi Nagashima, Keiko Nakayama

    PLoS Genetics　9　(8)　e1003698-e1003698　2013/08/29

    DOI： 10.1371/journal.pgen.1003698 　

    ISSN： 1553-7404

    eISSN： 1553-7404

  9. Opposing functions of Fbxw7 in keratinocyte growth, differentiation and skin tumorigenesis mediated through negative regulation of c-Myc and Notch Peer-reviewed

    Y. Ishikawa, M. Hosogane, R. Okuyama, S. Aoyama, I. Onoyama, K. I. Nakayama, K. Nakayama

    ONCOGENE　32　(15)　1921-1932　2013/04

    DOI： 10.1038/onc.2012.213 　

    ISSN： 0950-9232

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Presentations 24

  1. H3K27me3修飾パターン形成過程の時系列解析

    第37回日本分子生物学会年会　2014

  2. H3K27me3修飾パターン形成過程の時系列解析

    第37回日本分子生物学会年会　2014

  3. がん遺伝子Rasによる転写制御後にH3K27me3修飾変化が誘起される.

    第５回リトリート大学院生研究発表会　2012

  4. Change of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation.

    Winter Camp of GCOE 2012　2012

  5. がん遺伝子Rasによる転写変化後のH3K27me3修飾変化

    第36回日本分子生物学会年会　2012

  6. Change of Tri-methylation of H3K27 Occurs after Ras-mediated Transcriptional Regulation

    The 35th Annual Meeting of the Molecular Biology Society of Japan　2012

  7. がん遺伝子Rasによる転写制御後にH3K27me3修飾変化が誘起される.

    第５回リトリート大学院生研究発表会　2012

  8. Change of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation.

    Winter Camp of GCOE 2012　2012

  9. がん遺伝子Rasによる転写変化後のH3K27me3修飾変化

    第36回日本分子生物学会年会　2012

  10. Change of Tri-methylation of H3K27 Occurs after Ras-mediated Transcriptional Regulation

    The 35th Annual Meeting of the Molecular Biology Society of Japan　2012

  11. Ras-mediated regional silencing around Fas gene locus

    Winter Camp of GCOE 2011　2011

  12. H3K27 is tri-methylated after Ras-mediated regional silencing

    70th Annual Meeting of the Japanese Cancer Association　2011

  13. Changes of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation.

    The 5th International Workshop on Cell Regulations in Division and Arrest　2011

  14. Change of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation

    The 34th Annual Meeting of the Molecular Biology Society of Japan　2011

  15. Ras-mediated regional silencing around Fas gene locus

    Winter Camp of GCOE 2011　2011

  16. H3K27 is tri-methylated after Ras-mediated regional silencing

    70th Annual Meeting of the Japanese Cancer Association　2011

  17. Changes of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation.

    The 5th International Workshop on Cell Regulations in Division and Arrest　2011

  18. Change of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation

    The 34th Annual Meeting of the Molecular Biology Society of Japan　2011

  19. Ras-mediated regional silencing around Fas gene locus.

    Cold Spring Harbor Asia Conference Epigenetics, Chromatin & Transcription　2010

  20. がん遺伝子Rasは複数の遺伝子を含む広範囲な染色体領域を抑制する

    日本分子生物学会第10回春季シンポジウム　2010

  21. Ras-mediated gene silencing によるFas遺伝子領域のエピジェネティック制御

    第33回分子生物学会年会・第83回日本生化学会大会合同大会　2010

  22. Ras-mediated regional silencing around Fas gene locus.

    Cold Spring Harbor Asia Conference Epigenetics, Chromatin & Transcription　2010

  23. がん遺伝子Rasは複数の遺伝子を含む広範囲な染色体領域を抑制する

    日本分子生物学会第10回春季シンポジウム　2010

  24. Ras-mediated gene silencing によるFas遺伝子領域のエピジェネティック制御

    第33回分子生物学会年会・第83回日本生化学会大会合同大会　2010

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Research Projects 11

  1. 肝臓発生過程におけるリボソームヘテロジェネイティの機能解析

    細金 正樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  2. SETD5の膵臓癌における機能

    中山 啓子, 舟山 亮, 中川 直, 細金 正樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2021/04/01 - 2024/03/31

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    膵臓がん由来のRAS活性化型変異細胞（以降 PancCAと記載）のMEK阻害薬処理によって得られる阻害薬耐性細胞では、SETD5のタンパク質発現量が著しく増加することが報告されていた。 まず、この報告の再現性と汎用性の確認を行った。マウス膵臓がん由来のRAS活性化型変異細胞（KPC・AK4.4）を用いて、MEK阻害薬またはHDAC3阻害薬を添加し3日から12日間培養した。形態の変化や増殖の低下が観察されたがSETD5タンパク質蓄積を誘導することができなかった。これまでの報告とは、実験条件が多少異なっているが、一般的にRASの変異により増殖が活性化している腫瘍においてMEK阻害薬抵抗性獲得に、SETD5の発現量の変化は貢献していないと結論付けた。 これまでの我々は、神経細胞で、SETD5は細胞増殖に関わる分子の翻訳を制御していることを見出している。そこでRAS活性化型変異細胞においてもSETD5が同様の機能を有するのか調べることとした。CRISPR-Cas9システムを用いて、SDTD5を持たないRAS活性化型変異細胞（AK4.4-SETD5del）を作製した。In vitro の培養系では、AK4.4-SETD5del細胞は、野生型AK4.4に対して明らかな増殖の違いや、MEK阻害薬に対する感受性の違いを見出すことはできなかった。そこで、これらの細胞を同系統のマウス皮下に接種し、in vivo での腫瘍増殖能を調べたところ、AK4.4-SETD5delより発生した腫瘍は、野生型細胞より発生した腫瘍に比して、著しく腫瘍増大率が低下していることを見出した。

  3. Protein translation regulated by ribosome heterogeneity

    Hosogane Masaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2020/09 - 2022/03

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    It has been reported that tissue specific function of ribosome is in part regulated by tissue specific expression of ribosome components and accessory proteins. Among them, eukaryotic Translation Elongation Factor 1 Alpha 2 (eEF1A2) mutant mouse demonstrates severe phenotype in neurological development and is dead before maturation. This phenotype is explained by different expression pattern of its isoforms. eEF1A1 expresses ubiquitously among tissues, whereas eEF1A2 expresses only in brain, muscles and lymphoid tissues. To date, regulatory mechanisms of eEF1A2 have not been reported. To examine the mechanism of eEF1A2 in neural tissues, I established reporter cells of eEF1A2 expression by introducing EGFP under the control of eEF1A2 in Neuro2a neuroblastoma. With these cells, I screened shRNA library targeting more than 4,000 genes. With this strategy, I obtained candidate transcriptional factors of eEF1A2, including YY1.

  4. Verification of genomic diversity required for tumorigenesis

    NAKAYAMA Keiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2016/04/01 - 2017/03/31

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    CRISPR/Cas9 library was introduced to NIH3T3 cells and MDA-MD-468 cells to generate cell library which are gene disrupted. Groups of cells which was disrupted a gene by CRISPR/Cas9 system were obtained. These cells were inoculated subcutaneously on the back of immunodeficient mice to grow tumors. Even NIH3T3 cells which were introduced library failed to stable tumorigenesis as well as wild type cells. These data suggested that NIH3T3 population containing different kinds of a single gene disrupted cells did not achieve capability of tumorigenesis. With MDA-MD-462 cells, we observed cells introduced CRISPR/Cas9 library gain function of tumorigenesis compared to wild-type cells.

  5. Elucidation of transcriptional regulation by histone modification pattern

    NAKAYAMA Keiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2014/04/01 - 2017/03/31

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    TGF-β treatment to breast cancer cell lines induces epithelial-mesenchymal transition. We confirmed suppression of EZH2 expression by shRNA decreased modification levels of Histone H3K27me3. With this method, we analyzed the effect of suppression of H3K27me3 modification on transcript. Contrary to expectations, suppression of H3K27me3 did not cause a major effect. Next to breast cancer cell lines, we analyzed EZH2 deficient B lymphocytes. As we expected, modification of H3K27me3 in these downregulated and we obtained list of transcriptional activated genes. We also analyzed the modification level of H3K4me1 as a marker of enhancer activity. We identified the region where H3K4me1 increased after EZH2 deletion. However, we could not recognize which genes were regulated by corresponding enhancers.

  6. Genome wide analysis of epigenetic regulation of enhancer activity via H3K27 modifications

    HOSOGANE Masaki, NAKAYAMA Keiko, FUNAYAMA Ryo, SHIROTA Matuyuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2015/04 - 2017/03

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    It is still unknown whether H3K27me3 histone modification has a repressive role toward enhancer activity. To address this issue, we performed series of genome wide analysis to map and quantify H3K27me3, H3K27ac, p300 and mRNA expression in H3K27me3-depleted K562 human leukemia cells. We observed that the decrease in H3K27me3 level in enhancer region led to massive accumulation of H3K27ac and p300 at the same enhancer region, whereas the decrease in H3K27me3 in gene body was associated with upregulation of transcription of the same gene. Our results thus provide insights into the causal relationship between H3K27 histone modifications in regulatory elements and gene expression.

  7. Verification of genomic diversity required for tumorigenesis

    NAKAYAMA KEIKO, FUNAYAMA RYO, NAKAGAWA TADASHI, HOSOGANE MASAKI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2015/04/01 - 2016/03/31

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    It has been demonstrated that solid tumors are composed of various genomic mutated cells by genomic sequencing and analysis of diversity. In this program, we tried to identify critical mutations to generate solid tumors by random mutagenesis using CRISPR/Cas9 library. We used library which randomly made deletions at promoter regions of almost all reported human genes. We infected CRISPR/Cas9 library to human cancer cell lines to generate randomly mutated cell pool. Diversity of library extracted cell line were reduced within several days culture after introduction of library compared to that of original library. This observation suggest that in introduction of library make some clones die or proliferate less, as these clones have disadvantage to survival in vitro compared to other clones.

  8. Molecular mechanism of oncogenic RAS-induced gene silencing

    Funayama Ryo, NAKAYAMA Keiko, NAGASHIMA Takeshi, HOSOGANE Masaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2014/04/01 - 2016/03/31

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    Cancer is caused by DNA mutations. Some mutations cause alterations in gene expression, which result in abnormal growth and viability in cancer cells. We uncovered the molecular mechanism of transcriptional repression induced by an oncogenic RAS mutation, one of the most recurrent mutation in cancer. Phosphorylation activity of protein kinase Erk2 is required for RAS-induced transcriptional repression. Moreover, transcriptional repression triggers alteration of chromatin environment including histone modification.

  9. Regulation of celullar differentiation by degradation of core promoter recognition complex

    NAKAGAWA TADASHI, FUNAYAMA Ryo, HOSOGANE Masaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2013/08/30 - 2015/03/31

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    Cell differentiation accompanies global gene expression change. Previous studies revealed that genes to be expressed are determined by transcription factors, but emerging evidences indicate that the general transcription machinery is also involved in gene expression change. The general transcription machinery comprises several complexes, among which the promoter recognition complex TFIID plays a pivotal role in the selection of expressed genes. During the differentiation of myoblastic cell line and the epithelial-to-mesenchymal transition (EMT) of mammary epithelial cell line, several components of TFIID were found to be degraded by the ubiquitin-proteasome system. Induction of EMT caused the increase in an ubiquitin ligase which promoted the degradation of the TFIID component, leading to the reduction of translation-related gene expression. These results revealed a novel mechanism of regulation of the general transcription machinery by protein degradation during cell differentiation.

  10. A novel role of oncogenic RAS in gene silencing

    FUNAYAMA Ryo, NAGASHIMA Takeshi, HOSOGANE Masaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2012/04/01 - 2014/03/31

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    RAS-MAPK signaling regulates cell growth and survival. It is abnormally activated in cancer cells and represses transcription of tumor-suppressive genes to enhance tumorigenesis of the cells. In this study, I investigated the molecular mechanism of RAS-mediated transcriptional repression. RAS-MAPK signaling increases the amount of a histone modification in transcriptionally repressed genes. The alteration of the histone modification occurs after alteration of transcription, suggesting that the histone modification functions to maintain transcriptionally repressed state. Furthermore, I identified three chromatin proteins, which are required for transcriptional repression.

  11. がん遺伝子RasによるH3K27me3修飾制御機構の解析

    細金 正樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 東北大学

    2011 - 2012

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    ヒストンH3の27番目のリジンのトリメチル化修飾(H3K27me3)は転写抑制に関連するヒストン修飾として知られており、ヒトがんにおける異常な転写抑制に関与すると考えられている。しかしながら、がんの転写抑制と関連のあるH3K27me3修飾領域や、ヒストン修飾と転写制御の因果関係に関しては未だ不明な点が多い。そこで、本研究では、がんで高頻度に変異が見つかるシグナル伝達分子RasによるH3K27me3修飾変化に着目し、Rasによる修飾変化部位の同定を行い、修飾変化と転写制御との因果関係の検討をおこなった。 次世代シーケンス解析を用いたH3K27me3修飾変化領域の同定、および、同定された修飾領域と遺伝子発現の時系列変化の解析から、Rasによる転写変化がヒストン修飾変化に先行する遺伝子を複数同定した。この結果は、H3K27me3修飾変化は転写抑制と相関があるものの、転写変化の結果として誘起されることを示しており、RasによるH3K27me3修飾制御の新しい機能を示唆していた。そこで、当初計画していたRas下流のリン酸化酵素によるH3K27me3修飾酵素群の活性制御の研究から計画転換し、Ras活性化後のH3K27me3修飾の時系列変化の次世代シーケンス解析を行った。 その結果、ゲノムワイドに時系列変化を解析することで、H3K27me3修飾変化は転写変化の原因ではなく、むしろRasシグナルによる転写変化自体がH3K27me3修飾変化の原因であることが明らかとなった。これまで、ヒトがんにおいてヒストン修飾異常と転写異常が報告されているが、ヒトがんサンプルを用いた解析では転写とヒストン修飾の経時変化の情報が不足している。今後、本研究成果をヒトがんの解析へと発展させ、ヒトがんにおいてもRasによるH3K27me3修飾変化がRasによる転写異常に起因するものか検証することが必要と考えられた。

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