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Published on: April 21, 2023
Broad-Stroke Regulation by DNA Sequence-Specific Transcription Factors
Zachary Bigelow1, Sergei Nechaev2
1University of North Dakota, School of Medicine and Health Sciences, Grand Forks, North Dakota, United States; zachary.bigelow@und.edu.
Summary
Transcription factors (TFs) regulate gene expression beyond promoter binding. New evidence shows TFs function with limited DNA sequence dependence, impacting gene regulation post-initiation, especially during RNA polymerase II pausing.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Transcription factors (TFs) are key regulators of gene expression.
- Traditionally, TFs bind specific DNA motifs at gene promoters to control transcription.
- Emerging evidence reveals TF binding and function beyond these established paradigms.
Purpose of the Study:
- To examine findings supporting TFs regulating transcription with reduced DNA sequence dependence.
- To explore TF roles in gene regulation post-initiation, focusing on RNA polymerase II (Pol II) pausing.
- To discuss mechanisms and biological roles of sequence-independent TF functions.
Main Methods:
- Literature review and synthesis of existing research findings.
- Analysis of studies on TF binding outside of canonical promoter motifs.
- Examination of evidence for TFs acting post-transcriptional initiation.
Main Results:
- Widespread TF binding occurs outside of promoters and without cognate motifs.
- TFs can function without direct DNA binding.
- Mechanisms like cofactor/chromatin interactions and condensate formation facilitate TF binding and function.
Conclusions:
- TF regulation of transcription is not solely promoter-centric or sequence-dependent.
- Mechanisms enabling non-canonical TF binding are crucial for genome-wide transcription coordination.
- Understanding these extended functions is vital for comprehending gene regulation.
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