Nitika Gaurav, Akinori Kanai, Catherine Lachance, Khan L. Cox, Jiuyang Liu, Adrian T. Grzybowski, Nehmé Saksouk, Brianna J. Klein, Yosuke Komata, Shuhei Asada, Alexander J. Ruthenburg, Michael G. Poirier, Jacques Côté, Akihiko Yokoyama, Tatiana G. Kutateladze
{"title":"通过 JADE 亚基引导 HBO1 复合物的功能。","authors":"Nitika Gaurav, Akinori Kanai, Catherine Lachance, Khan L. Cox, Jiuyang Liu, Adrian T. Grzybowski, Nehmé Saksouk, Brianna J. Klein, Yosuke Komata, Shuhei Asada, Alexander J. Ruthenburg, Michael G. Poirier, Jacques Côté, Akihiko Yokoyama, Tatiana G. Kutateladze","doi":"10.1038/s41594-024-01245-2","DOIUrl":null,"url":null,"abstract":"JADE is a core subunit of the HBO1 acetyltransferase complex that regulates developmental and epigenetic programs and promotes gene transcription. Here we describe the mechanism by which JADE facilitates recruitment of the HBO1 complex to chromatin and mediates its enzymatic activity. Structural, genomic and complex assembly in vivo studies show that the PZP (PHD1–zinc-knuckle–PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA and is necessary for the association with chromatin targets. Recognition of unmethylated H3K4 by PZP directs enzymatic activity of the complex toward histone H4 acetylation, whereas H3K4 hypermethylation alters histone substrate selectivity. We demonstrate that PZP contributes to leukemogenesis, augmenting transforming activity of the NUP98–JADE2 fusion. Our findings highlight biological consequences and the impact of the intact JADE subunit on genomic recruitment, enzymatic function and pathological activity of the HBO1 complex. JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5000,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Guiding the HBO1 complex function through the JADE subunit\",\"authors\":\"Nitika Gaurav, Akinori Kanai, Catherine Lachance, Khan L. Cox, Jiuyang Liu, Adrian T. Grzybowski, Nehmé Saksouk, Brianna J. Klein, Yosuke Komata, Shuhei Asada, Alexander J. Ruthenburg, Michael G. Poirier, Jacques Côté, Akihiko Yokoyama, Tatiana G. Kutateladze\",\"doi\":\"10.1038/s41594-024-01245-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"JADE is a core subunit of the HBO1 acetyltransferase complex that regulates developmental and epigenetic programs and promotes gene transcription. Here we describe the mechanism by which JADE facilitates recruitment of the HBO1 complex to chromatin and mediates its enzymatic activity. Structural, genomic and complex assembly in vivo studies show that the PZP (PHD1–zinc-knuckle–PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA and is necessary for the association with chromatin targets. Recognition of unmethylated H3K4 by PZP directs enzymatic activity of the complex toward histone H4 acetylation, whereas H3K4 hypermethylation alters histone substrate selectivity. We demonstrate that PZP contributes to leukemogenesis, augmenting transforming activity of the NUP98–JADE2 fusion. Our findings highlight biological consequences and the impact of the intact JADE subunit on genomic recruitment, enzymatic function and pathological activity of the HBO1 complex. JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.\",\"PeriodicalId\":49141,\"journal\":{\"name\":\"Nature Structural & Molecular Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.5000,\"publicationDate\":\"2024-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Structural & Molecular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s41594-024-01245-2\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Structural & Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41594-024-01245-2","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Guiding the HBO1 complex function through the JADE subunit
JADE is a core subunit of the HBO1 acetyltransferase complex that regulates developmental and epigenetic programs and promotes gene transcription. Here we describe the mechanism by which JADE facilitates recruitment of the HBO1 complex to chromatin and mediates its enzymatic activity. Structural, genomic and complex assembly in vivo studies show that the PZP (PHD1–zinc-knuckle–PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA and is necessary for the association with chromatin targets. Recognition of unmethylated H3K4 by PZP directs enzymatic activity of the complex toward histone H4 acetylation, whereas H3K4 hypermethylation alters histone substrate selectivity. We demonstrate that PZP contributes to leukemogenesis, augmenting transforming activity of the NUP98–JADE2 fusion. Our findings highlight biological consequences and the impact of the intact JADE subunit on genomic recruitment, enzymatic function and pathological activity of the HBO1 complex. JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.
期刊介绍:
Nature Structural & Molecular Biology is a comprehensive platform that combines structural and molecular research. Our journal focuses on exploring the functional and mechanistic aspects of biological processes, emphasizing how molecular components collaborate to achieve a particular function. While structural data can shed light on these insights, our publication does not require them as a prerequisite.