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

Research Project

Project/Area Number 18K06188
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionInstitute 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
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsEpidermis / Keratinocyte / Epigenetics / 3D nuclear domain / Gene expression / Barrier function / Keratinocytes / Stratum granulosum / 3D nuclear regulation / Programmed cel death / Barrier Function / Transcription / 3D genome organization / Basal layer / Differentiated cells / DNA methylation / H3K27me3 / エピジェネティクス / 核内3次元構造 / 皮膚バリア機能 / 転写解析 / データ解析
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.

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.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2021

All Journal Article (1 results)

  • [Journal Article] A unique mode of keratinocyte death requires intracellular acidification2021

    • Author(s)
      Matsui T, Kadono-Maekubo N, Suzuki Y, Furuichi Y, Shiraga K, Sasaki H, Ishida A, Takahashi S, Okada T, Toyooka K, Sharif J, Abe T, Kiyonari H, Tominaga M, Miyawaki A, Amagai M
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 118 Issue: 17

    • DOI

      10.1073/pnas.2020722118

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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