调节因子ZFHX3通过AT动机驱动轴修改SCN中的昼夜功能
Michael J Parsons1, Marco Brancaccio2, Siddharth Sethi1
1MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK.
Cell
|August 2, 2015
概括
转录因子Zfhx3 (Zfhx3(Sci)) 的突变加速了小鼠的昼夜节律. 这种干扰会影响神经基因表达和昼夜节律的强度.
科学领域:
- 时间生物学
- 分子生物学
- 遗传学
背景情况:
- 上核 (SCN) 是哺乳动物的主生计时钟.
- 转录因子在调节昼夜基因表达方面发挥着至关重要的作用.
- 了解昼夜节律的分子机制对于解决睡眠和代谢障碍至关重要.
研究的目的:
- 研究Zfhx3转录因子在昼夜节律调节中的作用.
- 描述短路 (Zfhx3(Sci)) 突变对ZFHX3活动的功能影响.
- 在SCN中确定ZFHX3的下游目标.
主要方法:
- 在小鼠中识别和描述Zfhx3(Sci) 突变.
- 在体外测试以评估ZFHX3的DNA结合和转录激活.
- 用RNA测序分析SCN中的基因表达变化.
- 对SCN切片进行透视转导以研究昼夜调节.
主要成果:
- 在小鼠中,Zfhx3(Sci) 突变加速昼夜运动节律.
- 突变ZFHX3在目标基因,特别是神经基因中激活AT动机的能力降低.
- RNA测序显示神经基因表达的显著干扰对SCN信号的关键.
- 在突变的SCN切片中,ZFHX3对AT动机的循环调节显示出降低幅度和强度.
结论:
- Zfhx3(Sci) 突变揭示了一个涉及ZFHX3的新生日转录轴.
- 这一轴对于确定行为和分子昼夜节律的周期和强度至关重要.
- ZFHX3对神经基因表达的调节对于SCN细胞间通信和节律稳定至关重要.
更多相关视频
07:44In Vivo Monitoring of Circadian Clock Gene Expression in the Mouse Suprachiasmatic Nucleus Using Fluorescence Reporters
Published on: July 4, 2018
9.0K
06:53Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
8.9K
相关概念视频
Circadian Rhythms and Gene Regulation
4.7K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.7K
Circadian Rhythms and Gene Regulation
2.5K
2.5K
Biological Clocks and Seasonal Responses
42.1K
The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
42.1K
Master Transcription Regulators
8.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
Master Transcription Regulators
2.9K
2.9K
Regulation of Expression Occurs at Multiple Steps
4.3K
4.3K
