Deciphering the multi-scale, quantitative cis-regulatory code.
Mol Cell
; 83(3): 373-392, 2023 02 02.
Article
in En
| MEDLINE
| ID: mdl-36693380
ABSTRACT
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 relationships 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.
Key words
RNA polymerase II; activation domain; chromatin; cis-regulatory code; cis-regulatory element; coactivator; cofactor; corepressor; enhancer; gene regulation; insulator; nucleosome; pioneer factor; promoter; regulatory domain; repression domain; silencer; topologically associating domain; transcription; transcription factor
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Enhancer Elements, Genetic
Type of study:
Prognostic_studies
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2023
Document type:
Article
Affiliation country:
United States