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Deciphering the multi-scale, quantitative cis-regulatory code

delete2023-02-01
delete78
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OA
AI
S
Seungsoo Kim
J
Joanna Wysocka *
DOI:10.1016/j.molcel.2022.12.032delete
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Abstract

Abstract

En 中文
Uncovering the cis-regulatory code that governs when and how much each gene is transcribed in a given genome and cellular state remains a central goal of biology. Here, we discuss major layers of regulation that influence how transcriptional outputs are encoded by DNA sequence and cellular context. We first discuss how transcription factors bind specific DNA sequences in a dosage-dependent and cooperative manner and then proceed to the cofactors that facilitate transcription factor function and mediate the activity of modular cis-regulatory elements such as enhancers, silencers, and promoters. We then consider the complex and poorly understood interplay of these diverse elements within regulatory landscapes and its re-lationships with chromatin states and nuclear organization. We propose that a mechanistically informed, quantitative model of transcriptional regulation that integrates these multiple regulatory layers will be the key to ultimately cracking the cis-regulatory code.
Keywords:
TRANSCRIPTION FACTOR ACTIVITY
SUPER-ENHANCERS
GENE-EXPRESSION
SACCHAROMYCES-CEREVISIAE
PHENOTYPIC ROBUSTNESS
REVEALS PRINCIPLES
CHROMATIN DOMAINS
CELL IDENTITY
BINDING
PROMOTER

Journal

Molecular Cell cover
Molecular Cell
IF:
16.6
Papers:
1.0W
Citations:
8.5W

Organization

H
Howard Hughes Medical Institute
Scholars:
1.2W
Papers: 7.8K
Citations: 6.0W
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