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Published on: September 14, 2018
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DNA looping mediates cooperative transcription activation
Shu-Jing Han1, Yong-Liang Jiang2, Lin-Lin You3
1School of Life Sciences and Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science & Technology of China, Hefei, China.
Nature Structural & Molecular Biology
|January 4, 2024
Summary
Bacterial transcription factors NtcA and NtcB cooperate to activate RNA polymerase (RNAP) through a DNA looping mechanism. This process involves promoter DNA bending and looping, facilitating the assembly of transcription activation complexes (TACs).
Area of Science:
- Molecular Biology
- Structural Biology
- Microbiology
Background:
- Transcription factors regulate gene expression by binding to promoter regions.
- Cooperative binding of multiple transcription factors enhances gene activation efficiency.
- Understanding the molecular mechanisms of cooperative transcription is crucial for deciphering gene regulation.
Purpose of the Study:
- To elucidate the molecular mechanism of cooperative transcription activation by NtcA and NtcB in Anabaena.
- To determine the structural basis of transcription activation complex (TAC) formation.
- To investigate the role of DNA bending and looping in cooperative gene regulation.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine high-resolution structures of TACs.
- Biochemical assays to validate proposed mechanisms.
- Structural analysis of NtcA-TAC and NtcA-NtcB-TAC complexes.
Main Results:
- Two cryo-EM structures of Anabaena TACs were determined: NtcA-TAC and NtcA-NtcB-TAC.
- NtcA binding induces significant bending (∼50°) of the promoter DNA.
- Sequential binding of NtcA and NtcB leads to DNA looping, facilitating the assembly of a fully activated TAC with two activators.
Conclusions:
- A novel 'DNA looping' mechanism for cooperative transcription activation in bacteria is proposed.
- This mechanism explains how multiple transcription factors coordinate to efficiently activate RNA polymerase.
- The findings provide insights into the intricate regulation of gene expression in prokaryotes.
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