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Article: The elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer

TitleThe elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer
Authors
Keywordsoncohistone
breast cancer
ADAM
transcription
epigenetics
Issue Date2021
PublisherElsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology. The Journal's web site is located at https://www.journals.elsevier.com/journal-of-biological-chemistry
Citation
Journal of Biological Chemistry, 2021, v. 296, p. article no. 100374 How to Cite?
AbstractThe recent discovery of the cancer-associated E76K mutation in histone H2B (H2BE76-to-K) in several types of cancers revealed a new class of oncohistone. H2BE76K weakens the stability of histone octamers, alters gene expression, and promotes colony formation. However, the mechanism linking the H2BE76K mutation to cancer development remains largely unknown. In this study, we knock in the H2BE76K mutation in MDA-MB-231 breast cancer cells using CRISPR/Cas9 and show that the E76K mutant histone H2B preferentially localizes to genic regions. Interestingly, genes upregulated in the H2BE76K mutant cells are enriched for the E76K mutant H2B and are involved in cell adhesion and proliferation pathways. We focused on one H2BE76K target gene, ADAM19 (a disintegrin and metalloproteinase-domain-containing protein 19), a gene highly expressed in various human cancers including breast invasive carcinoma, and demonstrate that H2BE76K directly promotes ADAM19 transcription by facilitating efficient transcription along the gene body. ADAM19 depletion reduced the colony formation ability of the H2BE76K mutant cells, whereas wild-type MDA-MB-231 cells overexpressing ADAM19 mimics the colony formation phenotype of the H2BE76K mutant cells. Collectively, our data demonstrate the mechanism by which H2BE76K deregulates the expression of genes that control oncogenic properties through a combined effect of its specific genomic localization and nucleosome destabilization effect.
Persistent Identifierhttp://hdl.handle.net/10722/299262
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKang, TZE-
dc.contributor.authorZhu, L-
dc.contributor.authorYang, D-
dc.contributor.authorDing, D-
dc.contributor.authorZhu, X-
dc.contributor.authorWan, YCE-
dc.contributor.authorLiu, J-
dc.contributor.authorRamakrishnan, S-
dc.contributor.authorChan, LL-
dc.contributor.authorChan, SY-
dc.contributor.authorWang, X-
dc.contributor.authorGan, H-
dc.contributor.authorHan, J-
dc.contributor.authorIshibashi, T-
dc.contributor.authorLi, Q-
dc.contributor.authorChan, KM-
dc.date.accessioned2021-05-10T06:59:19Z-
dc.date.available2021-05-10T06:59:19Z-
dc.date.issued2021-
dc.identifier.citationJournal of Biological Chemistry, 2021, v. 296, p. article no. 100374-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/299262-
dc.description.abstractThe recent discovery of the cancer-associated E76K mutation in histone H2B (H2BE76-to-K) in several types of cancers revealed a new class of oncohistone. H2BE76K weakens the stability of histone octamers, alters gene expression, and promotes colony formation. However, the mechanism linking the H2BE76K mutation to cancer development remains largely unknown. In this study, we knock in the H2BE76K mutation in MDA-MB-231 breast cancer cells using CRISPR/Cas9 and show that the E76K mutant histone H2B preferentially localizes to genic regions. Interestingly, genes upregulated in the H2BE76K mutant cells are enriched for the E76K mutant H2B and are involved in cell adhesion and proliferation pathways. We focused on one H2BE76K target gene, ADAM19 (a disintegrin and metalloproteinase-domain-containing protein 19), a gene highly expressed in various human cancers including breast invasive carcinoma, and demonstrate that H2BE76K directly promotes ADAM19 transcription by facilitating efficient transcription along the gene body. ADAM19 depletion reduced the colony formation ability of the H2BE76K mutant cells, whereas wild-type MDA-MB-231 cells overexpressing ADAM19 mimics the colony formation phenotype of the H2BE76K mutant cells. Collectively, our data demonstrate the mechanism by which H2BE76K deregulates the expression of genes that control oncogenic properties through a combined effect of its specific genomic localization and nucleosome destabilization effect.-
dc.languageeng-
dc.publisherElsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology. The Journal's web site is located at https://www.journals.elsevier.com/journal-of-biological-chemistry-
dc.relation.ispartofJournal of Biological Chemistry-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectoncohistone-
dc.subjectbreast cancer-
dc.subjectADAM-
dc.subjecttranscription-
dc.subjectepigenetics-
dc.titleThe elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer-
dc.typeArticle-
dc.identifier.emailChan, SY: sychan@hkucc.hku.hk-
dc.identifier.authorityChan, SY=rp00356-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.jbc.2021.100374-
dc.identifier.pmid33548228-
dc.identifier.pmcidPMC7949156-
dc.identifier.scopuseid_2-s2.0-85102834194-
dc.identifier.hkuros322430-
dc.identifier.volume296-
dc.identifier.spagearticle no. 100374-
dc.identifier.epagearticle no. 100374-
dc.identifier.isiWOS:000672866400348-
dc.publisher.placeUnited States-

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