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Related Concept Videos

Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Transcription Factors02:16

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Master Transcription Regulators02:23

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Cis-regulatory Sequences02:02

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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...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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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...
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Updated: Aug 17, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Transcription Factor-Centric Approach to Identify Non-Recurring Putative Regulatory Drivers in Cancer.

Jingkang Zhao1,2, Vincentius Martin1,3, Raluca Gordân1,3,4,5

  • 1Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA.

Research in Computational Molecular Biology : ... Annual International Conference, RECOMB ... : Proceedings. RECOMB (Conference : 2005- )
|December 12, 2022
PubMed
Summary

Identifying non-coding mutations in cancer requires new methods. This study introduces a novel approach focusing on functional effects on gene regulation, rather than mutation recurrence, to find potential cancer drivers.

Keywords:
Combining p-valuesDNA-binding specificityEnhancers and promotersLiptak’s methodNon-coding mutationsRegulatory driversTranscription factors

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Area of Science:

  • Genomics
  • Cancer Biology
  • Bioinformatics

Background:

  • Millions of somatic mutations are found in cancer genomes, mostly non-coding.
  • Non-coding mutations can drive cancer by altering gene expression.
  • Current methods for identifying driver mutations rely on recurrence, which is limited for non-coding mutations.

Purpose of the Study:

  • To develop a new method for identifying regulatory driver mutations.
  • To assess the functional impact of non-coding mutations on transcription factor-DNA binding.
  • To identify genes dysregulated by non-coding mutations in liver cancer.

Main Methods:

  • Developed a method integrating mutation effects across regulatory regions for each gene.
  • Assessed if mutation effects on transcription factor-DNA binding are greater than expected by chance.
  • Applied the method to a liver cancer dataset with mutation and gene expression data.

Main Results:

  • Identified dozens of genes likely to have their regulation significantly perturbed by non-coding mutations.
  • Demonstrated that focusing on functional effects, not recurrence, can identify regulatory drivers.
  • Highlighted the potential of this approach for understanding non-coding mutation impacts.

Conclusions:

  • Functional effect analysis of non-coding mutations is a powerful strategy for identifying cancer drivers.
  • This method can reveal genes dysregulated by non-coding mutations in tumors.
  • The approach offers a new perspective beyond mutation recurrence for cancer genomics research.