Promoters and Transcription Factors

The DNA sequences that mark where transcription begins and the proteins that read them to switch genes on or off and tune their output.

Definition

A promoter is the DNA region that directs the start of transcription of a gene; transcription factors are proteins that bind promoter and enhancer sequences to recruit or modulate RNA polymerase, thereby controlling whether and how much a gene is transcribed.

Scope

This topic covers cis-acting DNA elements — core promoters, proximal elements, and distal enhancers — and the trans-acting proteins that bind them: general transcription factors required to position the polymerase and sequence-specific regulators that activate or repress particular genes. It addresses how these elements and factors combine to determine when and how strongly a gene is transcribed. The downstream logic of regulatory circuits is developed in the gene-regulation area.

Core questions

• What sequence elements define a promoter and where are they located?
• How do general transcription factors help position the polymerase?
• How do sequence-specific factors activate or repress particular genes?
• How do distant enhancers influence transcription at a promoter?

Key theories

Combinatorial control by transcription factors

A gene's transcription is set by the particular combination of activators and repressors bound at its promoter and enhancers, so a limited repertoire of factors can specify a large number of distinct expression patterns.

Modular cis-regulatory elements

Core promoters position the polymerase while separate proximal and distal elements such as enhancers bind regulatory factors and act at a distance, making regulatory DNA modular and combinable.

Mechanisms

General transcription factors assemble at the core promoter to recruit and correctly position RNA polymerase, forming the basal apparatus. Sequence-specific transcription factors bind their target sites at promoters and enhancers through DNA-binding domains and use separate activation or repression domains to recruit coactivators, corepressors, and chromatin-modifying complexes. Enhancers can act over long distances by looping the intervening DNA so that bound factors contact the basal apparatus, integrating many inputs into a single level of transcription.

Clinical relevance

Mutations in promoters, enhancers, and transcription factors cause developmental disorders and cancers, and transcription factors are intensively studied therapeutic targets; framed as significance rather than clinical guidance.

History

Analysis of bacterial and viral promoters in the 1970s and 1980s defined conserved promoter sequences, and the cloning of the first sequence-specific eukaryotic transcription factors established the combinatorial, modular view of gene control now standard in molecular biology.

Key figures

• Robert Tjian
• Mark Ptashne

Seminal works

• lodish2016
• alberts2014

Frequently asked questions

What is the difference between a promoter and an enhancer?

A promoter is the DNA next to the start site where the polymerase is positioned; an enhancer is a regulatory element, often far away, that boosts transcription through bound factors.

Do all transcription factors turn genes on?

No. Some are activators that increase transcription, while others are repressors that reduce or block it; the balance determines a gene's output.