Seven myths of how transcription factors read the cis-regulatory code.
Seven myths of how transcription factors read the cis-regulatory code.
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DOI：
10.1016/j.coisb.2020.08.002
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发表时间：
2020-10
影响因子：
3.7
通讯作者：
Zeitlinger J
中科院分区：
文献类型：
--
作者：
Zeitlinger J
现在正在从单细胞中大量生成高分辨率的基因组数据。它们提供了开发强大的机器学习算法（包括神经网络）的独特机会，以揭示顺式监管代码的规则。然而，当前的建模假设通常并非基于来自转录、发育遗传学、成像和结构研究的顺式调控密码的最新知识。在这里，我的目标是通过简要介绍该领域的历史概述、描述常见的误解并提供可能有助于指导计算方法的知识来填补这一空白。我将描述增强子活性的转录因子结合基序的组合要求所涉及的原理和机制，包括顺式调控密码中染色质可及性、阻遏物和低亲和力基序的作用。破译顺式调控密码将解锁基因组中的大量调控信息，并使我们能够定位与发育和疾病有关的顺式调控遗传变异。
Genomics data are now being generated at large quantities, of exquisite high resolution and from single cells. They offer a unique opportunity to develop powerful machine learning algorithms, including neural networks, to uncover the rules of the cis-regulatory code. However, current modeling assumptions are often not based on state-of-the-art knowledge of the cis-regulatory code from transcription, developmental genetics, imaging and structural studies. Here I aim to fill this gap by giving a brief historical overview of the field, describing common misconceptions and providing knowledge that might help to guide computational approaches. I will describe the principles and mechanisms involved in the combinatorial requirement of transcription factor binding motifs for enhancer activity, including the role of chromatin accessibility, repressors and low-affinity motifs in the cis-regulatory code. Deciphering the cis-regulatory code would unlock an enormous amount of regulatory information in the genome and would allow us to locate cis-regulatory genetic variants involved in development and disease.
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影响因子：
30.8
作者：
He, Qiye;Bardet, Anais F.;Zeitlinger, Julia
通讯作者：
Zeitlinger, Julia
影响因子：
46.9
作者：
Ernst J;Kellis M
通讯作者：
Kellis M
影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
影响因子：
46.9
作者：
He, Qiye;Johnston, Jeff;Zeitlinger, Julia
通讯作者：
Zeitlinger, Julia
单细胞染色质可及性揭示了调节变化的原理。
影响因子：
64.8
作者：
Buenrostro JD;Wu B;Litzenburger UM;Ruff D;Gonzales ML;Snyder MP;Chang HY;Greenleaf WJ
通讯作者：
Greenleaf WJ