MacroH2As regulate enhancer-promoter contacts affecting enhancer activity and sensitivity to inflammatory cytokines

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• dc.contributor.author Corujo, David
• dc.contributor.author Malinverni, Roberto
• dc.contributor.author Carrillo-Reixach, Juan
• dc.contributor.author Meers, Oliver
• dc.contributor.author Garcia-Jaraquemada, Arce
• dc.contributor.author Le Pannérer, Marguerite-Marie, 1990-
• dc.contributor.author Valero, Vanesa
• dc.contributor.author Pérez, Ainhoa
• dc.contributor.author Del Río-Álvarez, Álvaro
• dc.contributor.author Royo, Laura
• dc.contributor.author Pérez-González, Beatriz
• dc.contributor.author Raurell Vila, Helena
• dc.contributor.author Acemel, Rafael D.
• dc.contributor.author Santos-Pereira, José M.
• dc.contributor.author Gómez Skarmeta, José Luis
• dc.contributor.author Pasquali, Lorenzo
• dc.contributor.author Manyé, Josep
• dc.contributor.author Armengol, Carolina
• dc.contributor.author Buschbeck, Marcus
• dc.date.accessioned 2022-07-11T06:51:43Z
• dc.date.available 2022-07-11T06:51:43Z
• dc.date.issued 2022
• dc.description.abstract MacroH2A histone variants have a function in gene regulation that is poorly understood at the molecular level. We report that macroH2A1.2 and macroH2A2 modulate the transcriptional ground state of cancer cells and how they respond to inflammatory cytokines. Removal of macroH2A1.2 and macroH2A2 in hepatoblastoma cells affects the contact frequency of promoters and distal enhancers coinciding with changes in enhancer activity or preceding them in response to the cytokine tumor necrosis factor alpha. Although macroH2As regulate genes in both directions, they globally facilitate the nuclear factor κB (NF-κB)-mediated response. In contrast, macroH2As suppress the response to the pro-inflammatory cytokine interferon gamma. MacroH2A2 has a stronger contribution to gene repression than macroH2A1.2. Taken together, our results suggest that macroH2As have a role in regulating the response of cancer cells to inflammatory signals on the level of chromatin structure. This is likely relevant for the interaction of cancer cells with immune cells of their microenvironment.
• dc.description.sponsorship This research project was supported by the national grants RTI2018-094005-B-I00 and BFU2015-66559-P from FEDER / Ministerio de Ciencia e Innovación - Agencia Estatal de Investigación (to M.B.); PI09/00751 , PI10/02082 , and PI13/02340 from the Instituto de Salud Carlos III (to C.A.); the MECD fellowship FPU14/06542 (to D.C.); AGAUR 2019 FI_B01024 and 2022 FI_B00528 fellowships (to J.C.-R. and A.D.R.-A., respectively); and predoctoral fellowships BES-2016-077251 (to M.-M.L.P.) and PRE2019-088529 (to O.M.). Research in the M.B. lab is further supported by the following grants: the Marie Skłodowska Curie Training network “ INTERCEPT-MDS ” H2020-MSCA-ITN-2020-953407 (to M.B.); MINECO-ISCIII PIE16/00011 (to M.B.); the Deutsche José Carreras Leukämie Stiftung DJCLS 14R/2018 (to M.B.); AGAUR 2017-SGR-305 (to M.B.); and Fundació La Marató de TV3 257/C/2019 (to M.B.). C.A.’s research has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement nos. 668596 ( ChiLTERN ) and 826121 ( iPC ) as well as from CIBERehd ( CB06/04/0033 ) and AGAUR ( 2017-SGR-490 ). C.A. was supported by Ramón y Cajal ( RYC-2010-07249 ) of the Ministry of Science and Innovation of Spain. Research at the IJC is supported by the “ La Caixa” Foundation , the Fundació Internacional Josep Carreras , Celgene Spain , and the CERCA Programme / Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Corujo D, Malinverni R, Carrillo-Reixach J, Meers O, Garcia-Jaraquemada A, Le Pannérer MM, Valero V, Pérez A, Del Río-Álvarez Á, Royo L, Pérez-González B, Raurell H, Acemel RD, Santos-Pereira JM, Garrido-Pontnou M, Gómez-Skarmeta JL, Pasquali L, Manyé J, Armengol C, Buschbeck M. MacroH2As regulate enhancer-promoter contacts affecting enhancer activity and sensitivity to inflammatory cytokines. Cell Rep. 2022 Jun 21;39(12):110988. DOI: 10.1016/j.celrep.2022.110988
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2022.110988
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/53706
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep. 2022 Jun 21;39(12):110988
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/953407
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-094005-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-66559-P
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/668596
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/826121
• dc.rights © 2022 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword CP: Molecular biology
• dc.subject.keyword Cancer
• dc.subject.keyword Chromatin regulation
• dc.subject.keyword Epigenetics
• dc.subject.keyword Hepatoblastoma
• dc.subject.keyword Histone variants
• dc.subject.keyword Inflammation
• dc.subject.keyword MacroH2A
• dc.title MacroH2As regulate enhancer-promoter contacts affecting enhancer activity and sensitivity to inflammatory cytokines
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion