Annibali, V

Clerico, M

Cordero, F

Cutrupi, S

De Bortoli, M

Durelli, L

Ferrero, G

Iannello, A

Rolla, S

English

Institutional Research Information System University of Turin

14 December 2021AperTO - Archivio Istituzionale Open Access dell'Università di TorinoOriginal Citation:Estrogen receptor-alpha regulates epigenetic changes on genomic regulatory regions: potential biomarkers inmultiple sclerosis outcomesPublisher:Terms of use:Open Access(Article begins on next page)Anyone can freely access the full text of works made available as "Open Access". Works made available under aCreative Commons license can be used according to the terms and conditions of said license. Use of all other worksrequires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law.Availability:SAGE PUBLICATIONS LTDThis is a pre print version of the following article:This version is available http://hdl.handle.net/2318/1757444 since 2020-10-01T14:59:24ZAbstract: P948  Type: Poster  Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics  Background: Estrogen immunomodulation is associated with a reduction of relapse rate among women with multiple sclerosis (MS) during the third trimester of pregnancy. Estrogen Receptor-alpha (ERa) may regulate the differentiation of T cell subtypes, particularly of T regulatory (Treg) and Th17 cells.  Goals: Identification and validation of cell-type-specific genomic regulatory regions able to influence the proportion of Treg / Th17 cells of MS patients during pregnancy.  Material and methods: Peripheral blood mononuclear cells (PBMC) from 13 pregnant women patients 8 pregnant (8 MS and 5 healthy) were collected during the 3rd trimester of pregnancy and post-partum. Cell-type-specific regulatory regions have been identified by data integrative analysis on FoxP3 and RORc loci, coding for lineage-determining transcription factor of Treg and Th17 cell differentiation. Epigenetic modifications and ERa binding enrichment were evaluated by chromatin immunoprecipitation assay. RORc and FoxP3 promoter and genomic regulatory regions have been selected by bioinformatic analysis. In vitro analyses on purified Th17 and Tregs treated with E2 were conducted.  Results: ERa binds on RORc and FoxP3 promoter and genomic regulatory regions. On the third trimester of pregnancy, we observed that on Treg cells H3K4me3 on FoxP3, gene activation marker, is enriched more than H3K27me3, gene silencing marker; the ratio of H3K4me3/ H3K27me3 changed, in a similar way, in the post-partum. In vitro, the E2 treatment, induces, on cell-type-specific regulatory regions of purified and polarized Th17 cells the enrichment of H3K27me3, gene silencing marker, on RORc and the enrichment of H3K4me3, gene activation marker, of FoxP3.  Conclusion: ERa binds to regulatory regions of Foxp3 and RORC, driving the balance of Treg/Th17. This effect of E2 is confirmed in vitro. This result in a larger population of pregnant and non pregnant patients, could lead to the identification of new epigenomic biomarkers for monitoring disease outcomes and interferon treatment efficacy.  Disclosure:  This study is partially supported by grant from Merck Italy, an affiliate of Merck KGaA, Darmstadt, Germany.  Dr Clerico received personal compensation from Biogen Idec and Merck Serono for public speaking, editorial work and advisory boards.  Dr Cutrupi has nothing to disclose  Dr. Iannello has nothing to disclose  Dr. Ferrero has nothing to disclose  Dr. Cordero has nothing to disclose  Dr. Rolla has nothing to disclose  Dr. Annibali is an employee of Medical Affairs Division of Merck, Italy  Dr. De Bortoli has nothing to disclose  Dr Durelli received personal compensation from Biogen Idec and Merck Serono for public speaking, editorial work and advisory boards.  

Estrogen receptor-alpha regulates epigenetic changes on genomic regulatory regions: potential biomarkers in multiple sclerosis outcomes

https://iris.unito.it/bitstream/2318/1757444/1/Clerico%202016%20ECTRIMS.pdf

Estrogen receptor-alpha regulates epigenetic changes on genomic regulatory regions: potential biomarkers in multiple sclerosis outcomes

Abstract

Similar works

Full text

Available Versions

Institutional Research Information System University of Turin