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Updated: Aug 10, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Identification of a silencer module which selectively represses cyclic AMP-responsive element-dependent gene
1Department of Cellular and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Molecular and Cellular Biology
|November 1, 1995
Summary
A novel silencer element, LDH-NRE, negatively regulates cyclic AMP (cAMP)-inducible rat lactate dehydrogenase A (LDH A) gene transcription by interacting with transcription factors CREB and Fos.
Area of Science:
- Molecular Biology
- Gene Regulation
Background:
- The rat lactate dehydrogenase A (LDH A) gene promoter is regulated by cyclic AMP (cAMP).
- A distal negative regulatory element (LDH-NRE) has been identified that represses LDH A promoter activity.
Purpose of the Study:
- To characterize the function and mechanism of the LDH-NRE.
- To investigate the interaction of LDH-NRE with transcription factors involved in cAMP-responsive gene expression.
Main Methods:
- Reporter gene assays (LDH A/chloramphenicol acetyltransferase - CAT) were used to assess promoter activity.
- Gel mobility shift, footprinting, and Southwestern blotting identified binding proteins.
- Gel supershift assays determined the identity of the bound proteins.
Main Results:
- LDH-NRE functions as a silencer element, repressing both basal and cAMP-inducible transcription.
- LDH-NRE selectively represses cAMP-responsive element (CRE)-dependent transcription.
- A 69-kDa protein, identified as CREB and Fos or related proteins, binds specifically to LDH-NRE.
Conclusions:
- LDH-NRE negatively modulates cAMP-responsive LDH A transcription.
- LDH-NRE and CRE modules functionally interact through shared transacting factors.
- This interaction provides a mechanism for fine-tuning LDH A gene expression in response to cAMP signaling.
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