Reversible promoter methylation determines fluctuating expression of acute phase proteins.
Elife
; 92020 03 30.
Article
em En
| MEDLINE
| ID: mdl-32223889
Acute phase reactants (APRs) are secretory proteins exhibiting large expression changes in response to proinflammatory cytokines. Here we show that the expression pattern of a major human APR, that is C-reactive protein (CRP), is casually determined by DNMT3A and TET2-tuned promoter methylation status. CRP features a CpG-poor promoter with its CpG motifs located in binding sites of STAT3, C/EBP-ß and NF-κB. These motifs are highly methylated at the resting state, but undergo STAT3- and NF-κB-dependent demethylation upon cytokine stimulation, leading to markedly enhanced recruitment of C/EBP-ß that boosts CRP expression. Withdrawal of cytokines, by contrast, results in a rapid recovery of promoter methylation and termination of CRP induction. Further analysis suggests that reversible methylation also regulates the expression of highly inducible genes carrying CpG-poor promoters with APRs as representatives. Therefore, these CpG-poor promoters may evolve CpG-containing TF binding sites to harness dynamic methylation for prompt and reversible responses.
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Base de dados:
MEDLINE
Assunto principal:
Proteína C-Reativa
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Proteínas de Fase Aguda
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Regiões Promotoras Genéticas
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Metilação de DNA
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article