| First Author | Zhang L | Year | 2021 |
| Journal | Cell Death Dis | Volume | 12 |
| Issue | 5 | Pages | 476 |
| PubMed ID | 33980820 | Mgi Jnum | J:330291 |
| Mgi Id | MGI:6812245 | Doi | 10.1038/s41419-021-03761-1 |
| Citation | Zhang L, et al. (2021) CBP/p300 HAT maintains the gene network critical for beta cell identity and functional maturity. Cell Death Dis 12(5):476 |
| abstractText | Loss of beta cell identity and functional immaturity are thought to be involved in beta cell failure in type 2 diabetes. CREB-binding protein (CBP) and its paralogue p300 act as multifunctional transcriptional co-activators and histone acetyltransferases (HAT) with extensive biological functions. However, whether the regulatory role of CBP/p300 in islet beta cell function depends on the HAT activity remains uncertain. In this current study, A-485, a selective inhibitor of CBP/p300 HAT activity, greatly impaired glucose-stimulated insulin secretion from rat islets in vitro and in vivo. RNA-sequencing analysis showed a comprehensive downregulation of beta cell and alpha cell identity genes in A-485-treated islets, without upregulation of dedifferentiation markers and derepression of disallowed genes. A-485 treatment decreased the expressions of genes involved in glucose sensing, not in glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. In the islets of prediabetic db/db mice, CBP/p300 displayed a significant decrease with key genes for beta cell function. The deacetylation of histone H3K27 as well as the transcription factors Hnf1alpha and Foxo1 was involved in CBP/p300 HAT inactivation-repressed expressions of beta cell identity and functional genes. These findings highlight the dominant role of CBP/p300 HAT in the maintenance of beta cell identity by governing transcription network. |
