Jose-Mauricio Ayala
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Jose-Mauricio Ayala has a total of 5 co-authors. Here are the top co-authors by number of shared publications:
- Ana Victoria Ibarra-Meneses
Université de Montréal
1 shared publication - Christopher Fernandez-Prada
Université de Montréal
1 shared publication - David Langlais
Department of Human Genetics, Dahdaleh Institute of Genomic Medicine, McGill University
1 shared publication - Mathieu Mancini
McGill University Research Centre on Complex Traits, Montreal, QC, Canada
1 shared publication - Rebecca Bellworthy
Department of Human Genetics, Victor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, QC, Canada, H3A 0G1
1 shared publication
Latest Publications
- Open Access
Pioneer factor IRF1 unlocks latent enhancers to rewire chromatin and immunometabolism in inflammatory macrophages
Macrophages undergo extensive chromatin and metabolic remodeling to mount effective inflammatory responses. Here, we identify Interferon Regulatory Factor 1 (IRF1) as a pioneer factor that orchestrates these processes during IFNγ-driven macrophage activation. Integrative ATAC-seq, ChIP-seq, Hi-ChIP, and nascent RNA-seq demonstrated that IRF1 rapidly engages closed chromatin, initiates enhancer remodeling, and drives removal of repressive histone marks followed by deposition of activating modifications. IRF1-established enhancers form long-range chromatin interactions with target promoters, activating transcriptional programs that control immune effector functions, chromatin regulation, and cellular metabolism. Notably, IRF1 coordinates the IFNγ-induced metabolic switch from oxidative phosphorylation to aerobic glycolysis by transcriptionally regulating key metabolic enzymes, with metabolite profiles consistent with increased glycolysis and pentose phosphate pathway engagement, while remodeling the tricarboxylic acid (TCA) cycle to support immunometabolic outputs. IRF1-deficient macrophages fail to execute this coordinated metabolic reprogramming. High-density IRF1 motif arrays promote enhanced chromatin occupancy and recruitment of the BRG1-containing chromatin remodeling SWI/SNF complex. Pharmacologic inhibition of SWI/SNF ATPase activity (SMARCA2/4) disrupts IRF1-dependent chromatin remodeling and gene induction. Moreover, IRF1-induced enhancer states persist after IFNγ withdrawal, establishing durable epigenetic memory. Together, these findings establish IRF1 as a central integrator of chromatin remodeling, transcriptional control, and metabolic adaptation, linking pioneer-factor activity to macrophage plasticity and innate immune memory.
Open AccessPioneer factor IRF1 unlocks latent enhancers to rewire chromatin and immunometabolism in inflammatory macrophages
Macrophages undergo extensive chromatin and metabolic remodeling to mount effective inflammatory responses. Here, we identify Interferon Regulatory Factor 1 (IRF1) as a pioneer factor that orchestrates these processes during IFNγ-driven macrophage activation. Integrative ATAC-seq, ChIP-seq, Hi-ChIP, and nascent RNA-seq demonstrated that IRF1 rapidly engages closed chromatin, initiates enhancer remodeling, and drives removal of repressive histone marks followed by deposition of activating modifications. IRF1-established enhancers form long-range chromatin interactions with target promoters, activating transcriptional programs that control immune effector functions, chromatin regulation, and cellular metabolism. Notably, IRF1 coordinates the IFNγ-induced metabolic switch from oxidative phosphorylation to aerobic glycolysis by transcriptionally regulating key metabolic enzymes, with metabolite profiles consistent with increased glycolysis and pentose phosphate pathway engagement, while remodeling the tricarboxylic acid (TCA) cycle to support immunometabolic outputs. IRF1-deficient macrophages fail to execute this coordinated metabolic reprogramming. High-density IRF1 motif arrays promote enhanced chromatin occupancy and recruitment of the BRG1-containing chromatin remodeling SWI/SNF complex. Pharmacologic inhibition of SWI/SNF ATPase activity (SMARCA2/4) disrupts IRF1-dependent chromatin remodeling and gene induction. Moreover, IRF1-induced enhancer states persist after IFNγ withdrawal, establishing durable epigenetic memory. Together, these findings establish IRF1 as a central integrator of chromatin remodeling, transcriptional control, and metabolic adaptation, linking pioneer-factor activity to macrophage plasticity and innate immune memory.