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Related Concept Videos

Transcription Factors02:16

Transcription Factors

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...
Transcription Factors02:16

Transcription Factors

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...
Co-activators and Co-repressors02:04

Co-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...
Co-activators and Co-repressors02:04

Co-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...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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...
General Transcription Factors01:30

General Transcription Factors

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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Related Experiment Video

Updated: Jun 5, 2026

An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
11:36

An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations

Published on: April 21, 2023

Autoimmune non-coding variants perturb transcription factor-cofactor complex assembly linked to enhancer activity.

Maryam Dashtiahangar1,2, Trevor Siggers1,2,3

  • 1Department of Biology, Boston University, Boston, MA, USA.

Biorxiv : the Preprint Server for Biology
|June 4, 2026
PubMed
Summary
This summary is machine-generated.

Autoimmune disease variants in non-coding DNA alter gene regulation by changing transcription factor (TF) and cofactor (COF) binding. Our study links these variant changes to altered enhancer activity, revealing mechanisms of disease.

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Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

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Related Experiment Videos

Last Updated: Jun 5, 2026

An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
11:36

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Published on: April 21, 2023

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07:05

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Published on: September 8, 2021

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
10:16

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • Autoimmune disease-associated variants are primarily in non-coding DNA.
  • Mechanisms linking these variants to gene regulation are poorly understood.
  • Determining how disease alleles affect transcription factor (TF) binding, cofactor (COF) recruitment, and enhancer activity at scale is a challenge.

Purpose of the Study:

  • To profile differential TF and COF binding to autoimmune disease-associated variants.
  • To link altered TF/COF binding to enhancer activity and gene regulation.
  • To identify specific TFs, COFs, and regulatory modules involved in autoimmune disease pathogenesis.

Main Methods:

  • Utilized the CASCADE method to profile TF and COF binding to 2,901 autoimmune disease-associated variants in Jurkat T cells.
  • Integrated biochemical binding data with MPRA (Massively Parallel Reporter Assay) and allele-specific reporter expression data.
  • Analyzed binding patterns of five major TF families (ETS, RUNX, SP/KLF, OVOL/MYBL, bHLH) and associated cofactors.

Main Results:

  • Identified 516 variants that modulate TF/COF binding.
  • Found strong concordance between binding-modulating variants and expression-modulating variants.
  • Observed distinct binding enrichment for ETS and RUNX factors and identified allele-dependent regulator switching.
  • Discovered a recurrent regulatory module involving FOXM1 and cofactors (TIP60, BRD4, NCOA3, NCOA1) at ETS sites.

Conclusions:

  • Established a framework linking allele-specific TF/COF binding mechanisms to enhancer activity for prioritizing autoimmune disease variants.
  • Demonstrated that variants perturbing TF/COF binding are functionally relevant to gene regulation in T cells.
  • Highlighted the roles of specific TF families and cofactor complexes in autoimmune disease mechanisms.