Related Experiment Video
Updated: Jul 8, 2026
11:02
Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
Published on: May 27, 2016
CtBP is an essential corepressor for BCL6 autoregulation
Lourdes M Mendez1, Jose M Polo, J Jessica Yu
1Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. hye@aecom.yu.edu
Molecular and Cellular Biology
|January 24, 2008
Summary
C-terminal binding protein (CtBP) is a novel corepressor for the BCL6 transcription factor. CtBP is essential for BCL6 autoregulation in germinal center B cells, offering new therapeutic targets for BCL6-driven lymphomas.
Area of Science:
- Molecular Biology
- Immunology
- Cancer Biology
Background:
- The transcription repressor BCL6 is crucial for germinal center (GC) formation and function.
- GC B-cell lymphomas often exhibit sustained BCL6 expression due to genetic alterations bypassing its autoregulation.
- Previous research indicated lymphoma-associated BCL6 alterations disrupt its negative autoregulatory loop.
Purpose of the Study:
- To identify novel corepressors involved in BCL6 autoregulation.
- To investigate the role of CtBP in BCL6 transcriptional control.
- To explore the implications of CtBP-mediated BCL6 regulation in BCL6-driven lymphomas.
Main Methods:
- Investigated BCL6 autoregulation independence from known corepressor complexes (SMRT, NRC, BCOR, MTA3/NuRD).
- Assessed in vitro and in vivo interactions between BCL6 and CtBP.
- Utilized small interfering RNA (siRNA) to knock down CtBP in lymphoma cell lines with BCL6 translocations.
Main Results:
- BCL6 autoregulation was found to be independent of several established corepressor complexes.
- BCL6 directly interacts with CtBP, recruiting it to the 5' regulatory region.
- CtBP knockdown selectively relieved repression of the wild-type BCL6 allele but not translocated alleles in lymphoma cells.
Conclusions:
- CtBP is identified as a novel corepressor for BCL6.
- A unique corepressor requirement for BCL6 autoregulation may enable differential gene expression control in GC B cells.
- Targeting the BCL6-CtBP interaction could be a strategy for treating BCL6-driven lymphomas.
Related Concept Videos
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.