| Histone phosphorylation integrates the hepatic glucagon-PKA-CREB gluconeogenesis program in response to fasting |
| 論文作者 |
Zhao, YX; Li, S; Chen, YH; Wang, YC; Wei, YD; Zhou, TT; Zhang, YW; Yang, YY; Chen, LL; Liu, Y; Hu, C; Zhou, B; Ding, QR |
| 期刊/會議名稱 |
MOLECULAR CELL |
| 論文年度 |
2023 |
| 論文類別 |
Article |
| 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 14-3-3z, 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 phos-phomimic 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. |
| 期 |
7 |
| 卷 |
83 |
| 影響因子 |
16 |
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