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研究揭示人类基因调控元件的序列决定因素
作者:小柯机器人 发布时间:2022/2/27 13:47:19

芬兰赫尔辛基大学Jussi Taipale研究组揭示人类基因调控元件的序列决定因素。该项研究成果于2022年2月21日在线发表在《自然—遗传学》杂志上。

研究人员使用大规模平行报告试验(MPRA)测量了比人类基因组大约100倍序列空间的DNA序列转录活性。机器学习模型显示,转录因子(TF)通常以加法方式作用,语法较弱,大多数增强子通过一种似乎不涉及特定TF-TF相互作用的机制增加来自启动子的表达。增强子本身可分为三种类型:经典型、封闭染色质型和染色质依赖型。结果还表明,很少有TF在一个细胞中具有强烈的活性,大多数活性在不同的细胞类型之间是相似的。单个TF可以有多种基因调控活动,包括染色质开放和增强,促进和决定转录起始点(TSS)活性,这与TF结合模体是基因表达的关键原子单元的观点一致。

据悉,DNA可以决定基因表达的位置和时间,但控制基因表达的全部序列决定因素是未知的。

附:英文原文

Title: Sequence determinants of human gene regulatory elements

Author: Sahu, Biswajyoti, Hartonen, Tuomo, Pihlajamaa, Pivi, Wei, Bei, Dave, Kashyap, Zhu, Fangjie, Kaasinen, Eevi, Lidschreiber, Katja, Lidschreiber, Michael, Daub, Carsten O., Cramer, Patrick, Kivioja, Teemu, Taipale, Jussi

Issue&Volume: 2022-02-21

Abstract: DNA can determine where and when genes are expressed, but the full set of sequence determinants that control gene expression is unknown. Here, we measured the transcriptional activity of DNA sequences that represent an ~100 times larger sequence space than the human genome using massively parallel reporter assays (MPRAs). Machine learning models revealed that transcription factors (TFs) generally act in an additive manner with weak grammar and that most enhancers increase expression from a promoter by a mechanism that does not appear to involve specific TF–TF interactions. The enhancers themselves can be classified into three types: classical, closed chromatin and chromatin dependent. We also show that few TFs are strongly active in a cell, with most activities being similar between cell types. Individual TFs can have multiple gene regulatory activities, including chromatin opening and enhancing, promoting and determining transcription start site (TSS) activity, consistent with the view that the TF binding motif is the key atomic unit of gene expression.

DOI: 10.1038/s41588-021-01009-4

Source: https://www.nature.com/articles/s41588-021-01009-4

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex