H3K27Ac modification and gene expression in psoriasis.

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

Journal

Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 21 04 2021
revised: 19 06 2021
accepted: 04 07 2021
pubmed: 21 7 2021
medline: 27 1 2022
entrez: 20 7 2021
Statut: ppublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 METHODS
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 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 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.

Identifiants

pubmed: 34281744
pii: S0923-1811(21)00149-3
doi: 10.1016/j.jdermsci.2021.07.003
pii:
doi:

Substances chimiques

Transcription Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

93-100

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest All Authors state that they do not have any conflicts of interest within this manuscript.

Auteurs

Moamen Masalha (M)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel; Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Iddo Z Ben-Dov (IZ)

Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.

Oren Ram (O)

The Silberman Institute of Life Sciences and the Edmond and Lily Safra Center for Brain Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem, Israel.

Tal Meningher (T)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.

Jasmine Jacob-Hirsch (J)

Center for Cancer Research Sheba Medical Center, Tel Hashomer, Israel.

Riad Kassem (R)

Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel.

Yechezkel Sidi (Y)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel; Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: yehezkel.sidi@sheba.health.gov.il.

Dror Avni (D)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel; Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: droravni@msn.com.

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