Enhancer | 增强子 专题

Posted 2021-11-26 leezx

要做就做深做精！

 

问题：

什么是enhancer？一般多长？enhancer可能会出现在基因组的哪些区域？promoter呢？

enhancer和promoter的关系？enhancer、promoter、TF和RNA聚合酶II是如何在一起作用的？

enhancer如何影响基因表达？

如何鉴定enhancer？为什么ChiP-seq和ATAC-seq主要是用来测enhancer的？为什么enhancer的研究比promoter的更多？

什么是Enhancer RNA（eRNA）？

SNP是如何通过影响enhancer来影响转录调控，并最终影响基因表达的？

 

pic from General transcription factor - wiki

 

一般的解答：

打开wiki，enhancer首先是一段基因组上的DNA序列，它可以与蛋白（激活子、特指TF转录因子）结合，来增加某个基因的转录。enhancer的归类是cis-acting。长度通常在50-1500bp，坐标通常是在不固定的，可以在近端也可以在远端。在远端主要是可以通过DNA的折叠来在空间上接近要调控的基因。enhancer既可能在其调控基因的upstream，也可能在downstream。enhancer也可能在intron里面。enhancer的方向的正反并不会影响其功能。enhancer也有可能在不相关基因的exon里。Enhancers do not act on the promoter region itself, but are bound by activator proteins. These activator proteins interact with the mediator complex, which recruits polymerase II and the general transcription factors which then begin transcribing the genes.

确定enhancer的位置至关重要！我们暂时不考虑exon里面的enhancer，因为这在我们做eRNA表达的时候无法区分。所以我只需要过滤掉与exon有交集的exon即可。

打开wiki，promoter俗称启动子，是转录起始的关键，位置也比较固定，一般在其gene的TSS上游，同一条链上，长度一般是100-1000bp。

理一理，一个基因要想转录，RNA聚合酶是少不了的，必须在启动的时候结合到gene附件的DNA链上，那怎么结合的呢？promoter就是用于把RNA聚合酶锚定到DNA上的，promoter也可以通过motif来链接TF来召集RNA聚合酶，enhancers, silencers和insulators都是通过promoter来影响基因的转录和表达的。

打开wiki，Enhancer RNAs (eRNAs) represent a class of relatively short non-coding RNA molecules (50-2000 nucleotides) transcribed from the DNA sequence of enhancer regions. They were first detected in 2010 through the use of genome-wide techniques such as RNA-seq and ChIP-seq.[1] eRNAs can be subdivided into two main classes: 1D eRNAs and 2D eRNAs, which differ primarily in terms of their size, polyadenylation state, and transcriptional directionality.[2] The expression of a given eRNA seems to correlate with the activity of its corresponding enhancer in a context-dependent fashion. Increasing evidence suggests that eRNAs actively play a role in transcriptional regulation in cis and in trans, and while their mechanisms of action remain unclear, a few models have been proposed.[2]

 

enhancer的分析实例：

文献导读 | A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

 

 

参考资料：

notebook：http://localhost:8888/tree/human/enhancer