E2 Regulates Epigenetic Signature on Neuroglobin Enhancer-Promoter in Neuronal Cells.
Estrogens are neuroprotective factors in several neurological diseases. Neuroglobin (NGB) is one of the estrogen target genes involved in neuroprotection, but little is known about its transcriptional regulation. Estrogen genomic pathway in gene expression regulation is mediated by estrogen receptors (ERα and ERβ) that bind to specific regulatory genomic regions. We focused our attention on 17β-estradiol (E2)-induced NGB expression in human differentiated neuronal cell lines (SK-N-BE and NT-2). Previously, using bioinformatics analysis we identified a putative enhancer in the first intron of NGB locus. Therefore, we observed that E2 increased the enrichment of the H3K4me3 epigenetic marks at the promoter and of the H3K4me1 and H3K27Ac at the intron enhancer. In these NGB regulatory regions, we found estrogen receptor alpha (ERα) binding suggesting that ERα may mediate chromatin remodeling to induce NGB expression upon E2 treatment. Altogether our data show that NGB expression is regulated by ERα binding on genomic regulatory regions supporting hormone therapy applications for the neuroprotection against neurodegenerative diseases.
Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of TurinTurin, Italy; Department Neurosciences, University of TurinTurin, Italy.
Michela
M
Guglielmotto
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy.
Stefania
S
Reineri
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy.
Andrea
A
Iannello
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy; Department of Computer Science, University of TurinTurin, Italy.
Giulio
G
Ferrero
Center for Molecular Systems Biology, University of Turin Orbassano, Turin, Italy.
Ludovica
L
Vanzan
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy.
Valentina
V
Miano
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy.
Laura
L
Ricci
Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of TurinTurin, Italy; Department Neurosciences, University of TurinTurin, Italy.
Elena
E
Tamagno
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy.
Michele
M
De Bortoli
Center for Molecular Systems Biology, University of TurinOrbassano, Turin, Italy; Department of Clinical and Biological Sciences, University of TurinOrbassano, Turin, Italy.
Santina
S
Cutrupi
chromatin remodeling; epigenetic regulation; estrogen receptor; genomic regions; neuroglobin