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.
Abbreviations:
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)Keywords
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Article info
Publication history
Published online: July 06, 2021
Accepted:
July 4,
2021
Received in revised form:
June 19,
2021
Received:
April 21,
2021
Identification
Copyright
© 2021 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.
