KRAB指蛋白对基因调节网络的演变有所贡献
Michaël Imbeault1, Pierre-Yves Helleboid1, Didier Trono1
1School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Nature
|March 9, 2017
概括
克鲁佩尔相关盒 (KRAB) 域含指蛋白 (KZFPs) 与可转移元素一起进化,形成特定物种的表观遗传调节. 这些KZFP利用古老的遗传入侵者进行基因调控,
科学领域:
- 进化基因组学
- 表观遗传学
- 基因调节
背景情况:
- 包含克鲁佩尔相关盒子 (KRAB) 域的指蛋白 (KZFP) 是人类基因组中快速演变的基因家族编码的.
- 已知KZFPs通过TRIM28和H3K9me3依赖的异染色体形成抑制胚胎干细胞 (ES) 中的可移植元素.
- 假设宿主和可转移元素之间的进化军备竞赛驱动了KZFP基因选择.
研究的目的:
- 使用遗传学和基因组方法研究脊椎动物中KZFP基因的进化出现.
- 识别人类基因组中的KZFP目标并了解它们的功能作用.
- 阐明KZFPs,可转移元素和表观遗传调节之间的相互作用.
主要方法:
- 对KZFP基因的进化史进行基因分析.
- 基因组研究以确定人类基因组中的KZFP结合点.
- 分析KZFP与其他转录调节器之间的相互作用.
主要成果:
- KZFP家族的根源被重新分配到一个共同的祖先的鱼和四足动物.
- 大多数KZFP与可转化元素结合,其中一些显示正在进行的共同进化,但许多目标已经失去了转化潜力.
- KZFPs使用保存的可转移元素片段作为调节平台,表明其作用超出了最初的宿主-入侵者冲突.
结论:
- 对于KZFP和可转移的元素来说,这是一个长期的进化伙伴关系.
- KZFP有助于建立在很大程度上受物种限制的表观遗传调节层.
- 这项研究揭示了一种涉及古老遗传元素的新基因调节机制.
相关概念视频
02:02Cis-regulatory Sequences
12.0K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
12.0K
01:53Bacterial Transcription
37.5K
RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
37.5K
02:04Covalently Linked Protein Regulators
9.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.9K
02:04Covalently Linked Protein Regulators
2.1K
2.1K
02:36RNA Polymerase II Accessory Proteins
11.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
11.2K
02:04Co-activators and Co-repressors
8.8K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.8K