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Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
PU.1-mediated transcription is enhanced by HMG-I(Y)-dependent structural mechanisms
R T Lewis1, A Andreucci, B S Nikolajczyk
1Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
The Journal of Biological Chemistry
|January 1, 2001
Summary
High-mobility group protein I(Y) (HMG-I(Y)) enhances B cell-specific gene activation by altering the structure of the transcription factor PU.1. This protein-protein interaction increases PU.1
Area of Science:
- Molecular Biology
- Gene Regulation
- Protein-DNA Interactions
Background:
- The ets transcription factor PU.1 is crucial for immunoglobulin heavy chain gene regulation in B cells.
- Enhancer activation requires a multiprotein complex, including PU.1 and other factors.
- High-mobility group protein I(Y) (HMG-I(Y)) physically interacts with PU.1.
Purpose of the Study:
- To investigate the role of HMG-I(Y) in PU.1-mediated B cell-specific enhancer activation.
- To elucidate the mechanism by which HMG-I(Y) influences PU.1 binding to the mu enhancer.
- To determine if HMG-I(Y) acts as a coactivator in transcriptional regulation.
Main Methods:
- Protein-DNA binding assays to assess PU.1 affinity for the mu enhancer.
- Proteolytic mapping (trypsin and chymotrypsin) to detect structural changes in PU.1.
- Functional assays to evaluate HMG-I(Y)'s effect on transcriptional synergy between PU.1 and Ets-1.
Main Results:
- HMG-I(Y) increases PU.1 affinity for the mu enhancer muB element without altering DNA structure.
- Interaction with HMG-I(Y) induces a structural change in PU.1, making it more resistant to proteolysis.
- HMG-I(Y) enhances transcriptional synergy between PU.1 and Ets-1, indicating its role in the active enhancer complex.
Conclusions:
- HMG-I(Y) coactivates transcription by inducing a structural change in PU.1, enhancing its DNA binding affinity.
- This mechanism is particularly important for transcriptional activation when transcription factor concentrations are limiting, as seen with PU.1 in B cells.
- HMG-I(Y) represents a novel mechanism of coactivation through protein structure modulation.
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