Feola, Antonia (2015) cAMP-PKA regulate the interaction between histone demethylase, LSD1, estrogen receptor-α and the transcription initiation complex. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: cAMP-PKA regulate the interaction between histone demethylase, LSD1, estrogen receptor-α and the transcription initiation complex
Creators:
CreatorsEmail
Feola, Antoniatonia.feola@gmail.com
Date: 8 April 2015
Number of Pages: 63
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 27
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricoavvedim@unina.it
Tutor:
nomeemail
Porcellini, AntonioUNSPECIFIED
Date: 8 April 2015
Number of Pages: 63
Uncontrolled Keywords: estrogens-transcription-epigentic modifications-oxidation
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Aree tematiche (7° programma Quadro): SALUTE e TUTELA DEL CONSUMATORE > Biotecnologie, strumenti e tecnologie generiche per la salute umana
Additional Information: contact also Antonio.Porcellini@unina.it or Enrico V Avvedimento at avvedim@unina.it
Date Deposited: 09 Apr 2015 11:10
Last Modified: 07 May 2016 01:00
URI: http://www.fedoa.unina.it/id/eprint/10552
DOI: 10.6092/UNINA/FEDOA/10552

Abstract

ERα recruits co-activator and transcription factors to the Estrogen Responsive Elements (EREs) to induce transcription. Co-activator complexes facilitate transcriptional activation in part by interacting with chromatin remodeling and histone-modifying enzymes, which render the target chromatin permissive to transcriptional activation. One important protein is LSD1 or KDM1, a flavin adenine dinucleotide-dependent amine oxidase, that catalyzes the removal of methyl groups from di-methylated lysine 4 and lysine 9 in H3 histone, H3K4m2 and H3K9m2, to repress or induce transcription, respectively. The scope of this study is to determine whether cAMP and protein kinase A (PKA) regulate LSD1 and the initiation transcription complex formation. Our data demonstrate that cAMP-PKA phosphorylate LSD1 in threonine 110 and stimulate the interaction with active estrogen receptor α. This event is crucial for the assembly of the transcription initiation complex. We have mapped the region in the receptor necessary for this interaction and we have generated a mutant LSD1 that is not able to interact with the receptor and to stimulate estrogen-dependent transcription. PKA phosphorylates LSD1 at the mapped site (threonine 110) in vitro, and favors the recruitment of factors required for the transcription initiation complex formation. These data illustrate the interplay between two major signaling pathways, estrogens and cAMP-PKA, and how they regulate transcription initiation induced by estrogens.

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