H3K27Ac modification and gene expression in psoriasis

Moamen Masalha, Iddo Z. Ben-Dov, Oren Ram, Tal Meningher, Jasmine Jacob-Hirsch, Riad Kassem, Yechezkel Sidi*, Dror Avni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Numerous alterations in gene expression have been described in psoriatic lesions compared to uninvolved or healthy skin. However, the mechanisms which induce this altered expression remain unclear. Epigenetic modifications play a key role in regulating genes' expression. Only three studies compared the whole-genome DNA methylation of psoriasis versus healthy skin. The present is the first study of genome-wide comparison of histone modifications between psoriatic to healthy skins. Objective: Our objective was to explore the pattern of H3K27Ac modifications in psoriatic lesions compared to uninvolved psoriatic and healthy skin, in order to identify new genes involved in the pathogenesis of psoriasis. Method: Using ChIP-seq with anti H3K27Ac we compared the acetylation of lysine 27 on histone 3 (H3K27Ac) modification between psoriatic to healthy skins, combined with mRNA array. Results: We found a differential H3K27Ac pattern between psoriatic compared to uninvolved or healthy skins. We found that many of the overexpressed and H3K27Ac enriched genes in psoriasis, harbor a putative GRHL transcription factor-binding site. Conclusions: In the most overexpressed genes in psoriasis, there is an enrichment of H3K27Ac. However, the loss of H3K27 acetylation modification does not correlate with decreased gene expression. GRHL appears to play an important role in the pathogenesis of psoriasis and therefore, might be a new target for psoriasis therapeutics.

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalJournal of Dermatological Science
Volume103
Issue number2
DOIs
StatePublished - Aug 2021

Funding

FundersFunder number
Meir and Edith Rosenfeld Foundation
National Psoriasis Foundation
Israel Cancer Association20160038
Tel Aviv University
Council for Higher Education

    Keywords

    • Acetylation of the histone H3 at lysine 27 (H3K27Ac)
    • Chromatin immunoprecipitation sequencing (ChIP-seq)
    • Epigenetics
    • Psoriasis
    • Transcription factor

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