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

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 he...

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Detalles Bibliográficos
Autores: Corujo, David, Malinverni, Roberto, Carrillo-Reixach, Juan, Meers, Oliver, Garcia-Jaraquemada, Arce, Le Pannérer, Marguerite-Marie, 1990-, Valero, Vanesa, Pérez, Ainhoa, Del Río-Álvarez, Álvaro, Royo, Laura, Pérez-González, Beatriz, Raurell Vila, Helena, Acemel, Rafael D., Santos-Pereira, José M., Gómez Skarmeta, José Luis, Pasquali, Lorenzo, Manyé, Josep, Armengol, Carolina, Buschbeck, Marcus
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/53706
Acceso en línea:http://hdl.handle.net/10230/53706
http://dx.doi.org/10.1016/j.celrep.2022.110988
Access Level:acceso abierto
Palabra clave:CP: Molecular biology
Cancer
Chromatin regulation
Epigenetics
Hepatoblastoma
Histone variants
Inflammation
MacroH2A
Descripción
Sumario: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.

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