TCF4-HDAC4-CREB复合物对小鼠日睡眠量的转录调控。

IF 5.6 2区 医学 Q1 Medicine
Sleep Pub Date : 2025-05-12 DOI:10.1093/sleep/zsae313
Rui Zhou, Chaodong Zhang, Rui Gan, Xin Yin, Meng Wang, Bihan Shi, Lin Chen, Chongyang Wu, Qi Li, Qinghua Liu
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引用次数: 0

摘要

组蛋白去乙酰化酶HDAC4/5与cAMP反应元件结合蛋白(CREB)共同参与LKB1-SIK3激酶级联下游小鼠日睡眠量的转录调控。在这里,我们报道了小鼠基因组中CREB-和hdac4结合位点附近的碱性环-螺旋环(bHLH)蛋白的E-box基序的显著富集。腺相关病毒(AAV)介导的I类bHLH转录因子(如TCF4、TCF3或TCF12)在小鼠脑神经细胞中的表达减少了快速眼动睡眠(REMS)和非REMS (NREMS)的持续时间。TCF4需要bHLH结构域调节REMS或NREMS的量,其中后者大多与e -box结合活性无关。与TCF4通过bHLH结构域与CREB和HDAC4相互作用一致,TCF4依赖CREB和部分依赖HDAC4调节NREMS/REMS量。相反,CREB调节睡眠持续时间的能力也需要它与TCF4和HDAC4结合。综上所述,这些结果表明TCF4、HDAC4和CREB可能在小鼠日睡眠量的转录调控中协同起作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcriptional regulation of daily sleep amount by TCF4-HDAC4-CREB complex in mice.

Histone deacetylase HDAC4/5 cooperates with cAMP response element-binding protein (CREB) in the transcriptional regulation of daily sleep amount downstream of LKB1-SIK3 kinase cascade in mice. Here, we report a significant enrichment of the E-box motifs for the basic loop-helix-loop (bHLH) proteins near the CREB- and HDAC4-binding sites in the mouse genome. Adeno-associated virus-mediated expression of class I bHLH transcription factors, such as TCF4, TCF3, or TCF12, across the mouse brain neurons reduces the duration of rapid eye movement sleep (REMS) and non-REMS (NREMS). TCF4 requires its bHLH domain to regulate REMS or NREMS amount, of which the latter is mostly independent of the E-box-binding activity. Consistent with that TCF4 interacts with CREB and HDAC4 via the bHLH domain, TCF4 relies on CREB and partly on HDAC4 to regulate NREMS/REMS amount. Conversely, the ability of CREB to regulate sleep duration also requires its binding to TCF4 and HDAC4. Together, these results indicate that TCF4, HDAC4, and CREB could function cooperatively in the transcriptional regulation of daily sleep amount in mice.

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来源期刊
Sleep
Sleep Medicine-Neurology (clinical)
CiteScore
8.70
自引率
10.70%
发文量
0
期刊介绍: SLEEP® publishes findings from studies conducted at any level of analysis, including: Genes Molecules Cells Physiology Neural systems and circuits Behavior and cognition Self-report SLEEP® publishes articles that use a wide variety of scientific approaches and address a broad range of topics. These may include, but are not limited to: Basic and neuroscience studies of sleep and circadian mechanisms In vitro and animal models of sleep, circadian rhythms, and human disorders Pre-clinical human investigations, including the measurement and manipulation of sleep and circadian rhythms Studies in clinical or population samples. These may address factors influencing sleep and circadian rhythms (e.g., development and aging, and social and environmental influences) and relationships between sleep, circadian rhythms, health, and disease Clinical trials, epidemiology studies, implementation, and dissemination research.
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