Journal
CURRENT OPINION IN SYSTEMS BIOLOGY
Volume 23, Issue -, Pages 22-31Publisher
ELSEVIER
DOI: 10.1016/j.coisb.2020.08.002
Keywords
Transcription factors; Cis-regulatory code; Motif syntax; Chromatin accessibility; Cooperative binding; Low-affinity binding motif; Enhancer repression; Transcriptional regulatory networks
Funding
- Stowers Institute for Medical Research
- NIH [1R01HG010211]
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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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