Role of the epigenome and 3D nuclear dynamics in maintenance of skin barrier function

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: SHARIF Jafar 国立研究開発法人理化学研究所, 生命医科学研究センター, 専任研究員 (00577968)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Epidermis / Keratinocyte / Epigenetics / 3D nuclear domain / Gene expression

Outline of Final Research Achievements

Epidermis is the outermost layer of the skin that possess dual roles to protect the body from the outer environment (e.g. bacterial infection, temperature, dryness) and maintain of skin homeostasis. Specialized cell layers, namely, the basal layer and the cornified layer, plays a crucial role for regulation of epidermal functions. The molecular mechanisms that mediate the balance and function of these cell layers, however, remain unclear.
To elucidate how epigenetic mechanisms and 3D genome regulation changes between healthy or disease states epidermal cells, I have taken advantage of animal model systems. Using these systems, I have found that the onset of disease phenotype is associated with expression changes of genes involved in inflammation, immune response and keratinocyte differentiation. Importantly, these changes were regulated by H3K27me3 in an epigenetic level, and a shift from B-compartment (repressive state) to A-compartment (active state) revealed by Hi-C analysis.

Free Research Field

Epigenetics

Academic Significance and Societal Importance of the Research Achievements

My study shows that the barrier function of the epidermis is mediated by the expression a set of genes involved in immune response and cellular differentiation. Gene expression changes are regulated by changes in epigenetic marks (H3K27me3) and 3D nuclear domain.