基因调控中的信息整合和能源支出
Javier Estrada1, Felix Wong2, Angela DePace1
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|July 2, 2016
概括
细菌模型无法解释真核生物中的敏基因表达. 精确的基因调节和克服理论障碍的关键是能量消耗,而不仅仅是DNA结合.
科学领域:
- 分子生物学
- 生物物理
- 系统生物学
背景情况:
- 定量基因调节模型主要来自细菌系统.
- 现有的模型难以解释发育基因对转录因子 (TFs) 的快速表达模式.
研究的目的:
- 在真核生物中研究控制敏基因表达的物理原理.
- 确定细菌调节范式是否可以解释真核生物基因表达动态.
- 探索除了简单的TF结合之外的精确基因表达控制机制.
主要方法:
- 基于物理原理的理论建模.
- 分析跨多个转录因子结合点的信息整合.
- 在调节性DNA动力学中考虑热力学平衡和能量消耗 (动力学校对).
主要成果:
- 细菌范式不足以解释真核生物中的敏基因表达.
- 信息整合可以提高清晰度,但受到"霍普菲尔德障碍" (与希尔系数相关) 的限制.
- 通过动力校对等机制的能量消耗可以克服这一障碍,实现更高的表达清晰度.
结论:
- 细胞基因调节需要超出基于平衡的TF结合的机制.
- 能量依赖的过程对于实现发育所需的精确基因表达至关重要.
- 拟定一种包含物理原理的真核生物基因调节的新定量框架.
相关概念视频
Regulation of Metabolism
12.1K
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
12.1K
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
Energy Balance
1.4K
The human body gets energy from the three macronutrients: carbohydrates, proteins, and fats. Energy is released when the chemical bonds in the organic compounds present in the food are broken down. The energy content of food is measured in kilocalories (kcal), defined as the amount of heat required to raise the temperature of one kilogram of water by one degree Celsius. This value is determined by measuring the temperature change of the water surrounding a calorimeter after the complete...
1.4K
Structure of a Gene
16.6K
A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
16.6K
Regulation of Expression at Multiple Steps
1.5K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.5K


