CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.
CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.
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CBP/p300 HAT 维持对 β 细胞身份和功能成熟至关重要的基因网络
DOI：
10.1038/s41419-021-03761-1
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发表时间：
2021-05-12
影响因子：
9
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Zhang L;Sheng C;Zhou F;Zhu K;Wang S;Liu Q;Yuan M;Xu Z;Liu Y;Lu J;Liu J;Zhou L;Wang X
β细胞身份和功能不成熟的损失与2型糖尿病中的β细胞失败有关当前的研究，A-485， CBP/p300 HAT活性的选择性抑制剂，在体外和体内大鼠胰岛分泌的葡萄糖刺激性损害很大。参与葡萄糖传感的基因，而不是糖酵解，三核酸的基因循环和氧化性磷酸化。 CBP/P300 HAT在维持β细胞身份中的主要作用管理转录网络。
Loss of β cell identity and functional immaturity are thought to be involved in β 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 β 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 β cell and α 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 β cell function. The deacetylation of histone H3K27 as well as the transcription factors Hnf1α and Foxo1 was involved in CBP/p300 HAT inactivation-repressed expressions of β cell identity and functional genes. These findings highlight the dominant role of CBP/p300 HAT in the maintenance of β cell identity by governing transcription network.
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DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
5.3
作者：
Hussain, Mehboob A.;Porras, Delia L.;Wondisford, Fredric E.
通讯作者：
Wondisford, Fredric E.
慢性高血糖引发糖尿病动物模型胰腺β细胞分化丧失
影响因子：
4.8
作者：
Jonas, JC;Sharma, A;Weir, GC
通讯作者：
Weir, GC
影响因子：
4.8
作者：
Hussain, MA;Habener, JF
通讯作者：
Habener, JF
影响因子：
15.9
作者：
Dhawan, Sangeeta;Tschen, Shuen-Ing;Bhushan, Anil
通讯作者：
Bhushan, Anil