FAPESP-MRC: YEATS4-Histone Acylation axis in sex-dependent gene expression in intestinal homeostasis and disease

• Grant number: 25/07673-8
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2026
• End date: December 31, 2029
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Marco Aurélio Ramirez Vinolo
• Principal researcher abroad: Patrick Daniel Varga-Weisz
• Institution abroad: University Of Essex , England
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Associated researchers: Naiara Beraza ; Nicolae Radu Zabet ; Rodrigo Nalio Ramos ; Vinicius de Andrade Oliveira

Abstract

The gut microbiome has emerged as an important determinant of health and disease. An important set of diseases that link to the gut microbiome are inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. These diseases, in turn, predispose to cancer. YEATS4 is a chromatin protein found in mammals that has been strongly implicated to suppress cancer, but its mechanisms and roles in a tissue are not well understood. We propose that YEATS4 is a master regulator of sex hormone-dependent gene regulation in the gut and integrates microbial cues and cellular metabolism. We hypothesise that the role of a nexus of external stimuli and cellular metabolism, makes YEATS4 an important integrator for intestinal homeostasis, preventing inflammation, dysplasias and cancer. Therefore, it is critical to understand the role and mechanisms of this factor in a physiological, tissue context. To test this hypothesis and to unravel the molecular mechanisms of YEATS4, we will deliver a comprehensive analysis of function of YEATS4 in the intestine using state-of-the-art approaches: mouse models, gut organoid culture, single-cell transcriptomic approaches, chromatin analysis and biochemistry. In summary, we will elucidate biological mechanisms relevant to human health and disease, including cancer, by uncovering mechanisms and roles of sex dependent gene regulation through chromatin remodelling mechanisms, shedding light onto the role and function of an important chromatin factor in a relevant tissue, histone modification reader YEATS4. (AU)