生物
糖异生
奶油
组蛋白
组蛋白H3
CREB结合蛋白
胰高血糖素
磷酸化
内分泌学
内科学
细胞生物学
生物化学
新陈代谢
激素
转录因子
基因
医学
作者
Yongxu Zhao,Shuang Li,Yanhao Chen,Yuchen Wang,Yuda Wei,Tingting Zhou,Qian Zhang,Yuanyuan Yang,Lanlan Chen,Yan Liu,Cheng Hu,Ben Zhou,Qiurong Ding
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-04-01
卷期号:83 (7): 1093-1108.e8
被引量:6
标识
DOI:10.1016/j.molcel.2023.02.007
摘要
The glucagon-PKA signal is generally believed to control hepatic gluconeogenesis via the CREB transcription factor. Here we uncovered a distinct function of this signal in directly stimulating histone phosphorylation for gluconeogenic gene regulation in mice. In the fasting state, CREB recruited activated PKA to regions near gluconeogenic genes, where PKA phosphorylated histone H3 serine 28 (H3S28ph). H3S28ph, recognized by 14-3-3ζ, promoted recruitment of RNA polymerase II and transcriptional stimulation of gluconeogenic genes. In contrast, in the fed state, more PP2A was found near gluconeogenic genes, which counteracted PKA by dephosphorylating H3S28ph and repressing transcription. Importantly, ectopic expression of phosphomimic H3S28 efficiently restored gluconeogenic gene expression when liver PKA or CREB was depleted. These results together highlight a different functional scheme in regulating gluconeogenesis by the glucagon-PKA-CREB-H3S28ph cascade, in which the hormone signal is transmitted to chromatin for rapid and efficient gluconeogenic gene activation.
科研通智能强力驱动
Strongly Powered by AbleSci AI