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Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

10.9K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.9K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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...
8.4K
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

11.5K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.5K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

7.1K
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...
7.1K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Related Experiment Video

Updated: Jan 10, 2026

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
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In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

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Targeted Transcriptional Repression by Induced Proximity.

Christian E Stieger, Xinru Chen, Dustin Dovala

    Biorxiv : the Preprint Server for Biology
    |November 24, 2025
    PubMed
    Summary

    A new therapeutic approach called Transcriptional Regulation via Active Control of Epigenetic Reprogramming (TRACER) silences undruggable cancer-driving transcription factors by recruiting epigenetic repressors. This epigenetic reprogramming strategy offers a novel treatment for difficult-to-treat cancers.

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    Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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    In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
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    Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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    Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
    07:23

    Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

    Published on: June 15, 2016

    8.9K

    Area of Science:

    • Oncology
    • Epigenetics
    • Drug Discovery

    Background:

    • Many cancer-driving proteins, particularly transcription factors, are undruggable due to lack of pockets and reliance on protein-DNA/protein-protein interactions.
    • Transcription factors are challenging targets due to rapid turnover, resistance to inhibition, and evasion of protein degradation strategies.

    Purpose of the Study:

    • To introduce a novel induced-proximity therapeutic modality, TRACER, for targeted transcriptional silencing.
    • To demonstrate TRACER's efficacy in silencing estrogen receptor (ER) and androgen receptor (AR) in cancer models.

    Main Methods:

    • Development of small-molecule TRACERs to tether MBD2 and the NuRD complex to transcription factor ligands.
    • Application of ER-TRACER in breast cancer cells and AR-TRACER in prostate cancer cells.
    • Modular reprogramming of TRACERs to recruit alternative repressors like PRC2.

    Main Results:

    • ER-TRACER potently suppressed ER transcriptional activity and downregulated target genes in breast cancer, dependent on MBD2 and HDACs.
    • AR-TRACER achieved >90% inhibition of both full-length AR and AR-V7 activity in prostate cancer cells.
    • TRACERs demonstrated modularity, enabling recruitment of different corepressor complexes for targeted gene repression.

    Conclusions:

    • TRACERs represent a generalizable modality for pharmacologically silencing undruggable transcription factors via epigenetic reprogramming.
    • This approach offers a promising new strategy for treating cancers resistant to current therapies.