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.
Bibliographical noteFunding Information:
This work was supported by the: Israel Cancer Association (ICA) -grant number 20160038 to Avni D., and by National Psoriasis Foundation/USA to Avni D., and by The Meir and Edith Rosenfeld Foundation to Sidi Y. Masalha M. was award by the Scholarship of Constantiner Institute for Molecular Genetics of Tel Aviv University and The Lois and Martin Whitman Scholarship Fund and by Outstanding Doctoral Students of the Israeli Council for Higher Education .
- Acetylation of the histone H3 at lysine 27 (H3K27Ac)
- Chromatin immunoprecipitation sequencing (ChIP-seq)
- Transcription factor