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Related Concept Videos

Combinatorial Gene Control02:33

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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.
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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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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...
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Related Experiment Video

Updated: Jan 8, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Understanding Transcriptional Regulatory Redundancy by Learnable Global Subset Perturbations.

Junhao Liu1, Siwei Xu1, Dylan Riffle2

  • 1University of California, Irvine.

Proceedings of Machine Learning Research
|December 12, 2025
PubMed
Summary

We developed GRIDS, a computational method to identify cis-regulatory element (CRE) sets that work together to control gene expression. GRIDS reveals complex regulatory redundancy, advancing our understanding of cellular regulation.

Keywords:
Single-Cell Multi-OmicsTranscriptional Regulatory Factor

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Transcriptional regulation by cis-regulatory elements (CREs) is vital for biological functions.
  • Disruption of CREs can lead to diseases, and their redundancy necessitates methods to identify collaborative regulatory sets.
  • Understanding how CREs work together is key to deciphering gene expression control.

Purpose of the Study:

  • To introduce GRIDS, an in silico computational method for dissecting combinatorial CRE effects.
  • To identify sets of CREs that collaboratively regulate gene expression effectively, accounting for redundancy.
  • To provide global explanations of gene regulation by CREs.

Main Methods:

  • GRIDS employs a two-phase approach as a global feature explanation challenge.
  • It constructs a differentiable surrogate function to model complex gene regulatory processes and enable cross-modal translations.
  • Learnable perturbations within a state transition framework are used for efficient navigation of the combinatorial feature landscape.

Main Results:

  • GRIDS demonstrates superior explanatory capabilities compared to existing methods in comprehensive benchmarks.
  • Global explanations from GRIDS reveal intricate regulatory redundancy across diverse cell types and states.
  • The method effectively navigates the complex combinatorial feature landscape of CREs.

Conclusions:

  • GRIDS offers a powerful computational approach to understand combinatorial cis-regulatory element effects.
  • The findings highlight the significance of regulatory redundancy in cellular regulation.
  • GRIDS has the potential to significantly advance biological research in gene expression and disease mechanisms.