H3K27Ac modification and gene expression in psoriasis. Issue 2 (August 2021)

• Record Type: Journal Article
• Authors: Masalha, Moamen; Ben-Dov, Iddo Z.; Ram, Oren; Meningher, Tal; Jacob-Hirsch, Jasmine; Kassem, Riad; Sidi, Yechezkel; Avni, Dror
• Is Part Of: Journal of dermatological science. Volume 103:Issue 2(2021)
• Page Start: 93
• Page End: 100
• Publication Date: 2021-08
• Subjects: KC Keratinocytes -- H3K4me3 Trimethylation of Histone H3 at lysine 4 -- H4K20me1 Mono-methylation of Histone H4 at lysine 20 -- H3K79me1 Mono-methylation of Histone H3 at lysine 79 -- H3K27Ac Acetylation of the Histone H3 at lysine 27 -- H2BK5Ac Acetylation of the Histone H2B at lysine 5 -- TSS Transcription start site -- DMR Differentially methylated region -- TF Transcription factor -- bps Base pairs; Psoriasis -- Epigenetics -- Acetylation of the histone H3 at lysine 27 (H3K27Ac) -- Transcription factor -- Chromatin immunoprecipitation sequencing (ChIP-seq); Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2021.07.003
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: There is a differential H3K27Ac pattern between psoriatic to healthy skin. There is a differential H3K27Ac pattern between psoriatic to uninvolved skin. In most overexpressed genes in psoriasis, there is an enrichment of H3K27Ac. Decreased gene expression in psoriasis does not correlate with decreased H3K27Ac. Many psoriatic overexpressed and H3K27Ac enriched genes, have GRHL binding site. 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.