Authors: David Corujo, Roberto Malinverni, Juan Carrillo-Reixach, Oliver Meers, Arce Garcia-Jaraquemada, Marguerite-Marie Le Pannérer, Vanesa Valero, Ainhoa Pérez, Álvaro Del Río-Álvarez, Laura Royo, Beatriz Pérez-González, Helena Raurell, Rafael D.Acemel, José M.Santos-Pereira, Marta Garrido-Pontnou, José Luis Gómez Skarmeta, Lorenzo Pasquali, Josep Manyé, Carolina Armengol, Marcus Buschbeck

Institutions:

  • Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, Badalona, Barcelona 08916, Spain
  • Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Badalona, Barcelona 08916, Spain
  • Childhood Liver Oncology Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona 08916, Spain
  • Doctoral Programme in Biomedicine, Universitat de Barcelona, Facultat de Farmàcia i Ciències de l’Alimentació, Barcelona 08028, Spain
  • IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona 08916, Spain
  • PhD Programme in Biomedicine, Universitat Pompeu Fabra, Barcelona 08003, Spain
  • Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain
  • Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Universidad Pablo de Olavide-Junta de Andalucía, Sevilla 41013, Spain
  • Pathology Department, Hospital Vall d’Hebron, Barcelona 08035, Spain
  • Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), Madrid 28029, Spain

Publication: ScienceDirect

Date: June, 2022

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

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.