Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10799275 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | 2013 | 7 Pages |
Abstract
We have examined at the molecular level the crosstalk between these nuclear receptors from the point of view of their control of cell growth and show here that RA reverts estrogen-stimulated transcription of the pivotal anti-apoptotic bcl-2 gene by preventing demethylation of dimethyl lysine 9 in histone H3 (HeK9me2). As we previously reported, this is obtained by means of E2-triggered activation of the lysine-specific demethylase 1 (LSD1), an enzyme that manages chromatin plasticity in order to allow specific movements of chromosomal regions within the nucleus. We find that E2 fuels LSD1 by inducing migration of the catalytic subunit of protein kinase A (PKA) into the nucleus, where it targets estrogen-responsive loci. RA rescues LSD1-dependent disappearance of H3K9me2 at bcl-2 regulatory regions upon the prevention of PKA assembly to the same sites.
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Authors
Maria Neve Ombra, Annalisa Di Santi, Ciro Abbondanza, Antimo Migliaccio, Enrico Vittorio Avvedimento, Bruno Perillo,