Expression in T-cells of the proapoptotic protein p66SHC is controlled by promoter demethylation.
p66Shc plays a key role in oxidative stress-induced apoptosis. p66Shc gene expression is tissue-specific and controlled by promoter methylation. In T-cells p66Shc expression is induced by a variety of apoptotic stimuli. We have addressed the mechanisms regulating p66Shc expression in T-cells. We show that the increase in p66Shc protein following stimulation with a Ca2+ ionophore results from enhanced gene expression, which is primarily dependent on DNA replication-independent promoter demethylation. Our data underline the role of CpG methylation in the control of p66Shc gene expression and provide evidence that Ca2+ signaling may lead to epigenetic modifications in nondividing cells.
Pezzicoli
Alfredo
A
Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
Ulivieri
Cristina
C
Capitani
Nagaja
N
Ventura
Andrea
A
Pelicci
Piergiuseppe
P
Baldari
Cosima T
CT
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013601:T-Lymphocytes / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D007476:Ionophores; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000001:Calcimycin; D002118:Calcium