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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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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Related Experiment Video

Updated: Jun 25, 2025

Small RNA Transfection in Primary Human Th17 Cells by Next Generation Electroporation
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A proximal enhancer regulates RORA expression during early human Th17 cell differentiation.

Ubaid Ullah Kalim1, Rahul Biradar1, Sini Junttila1

  • 1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland.

Clinical Immunology (Orlando, Fla.)
|May 24, 2024
PubMed
Summary

Researchers identified key enhancers controlling T helper 17 (Th17) cell differentiation. They found autoimmune disease-associated genetic variants within these Th17 enhancers, including one regulating RORA, offering insights into Th17 cell fate.

Keywords:
AutoimmunityEnhancer mappingHuman Th17 cellsRORARegulatory SNPs

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Gene regulatory elements, like enhancers, are crucial for cell identity by modulating gene expression.
  • The dynamic changes in enhancer activity during human T helper 17 (Th17) cell differentiation are not fully understood.

Purpose of the Study:

  • To identify and characterize enhancers involved in Th17 cell differentiation.
  • To investigate the role of genetic variations within these enhancers in autoimmune diseases.
  • To elucidate the regulatory mechanism of RORA in Th17 cell development.

Main Methods:

  • Chromatin accessibility profiling using ATAC-seq.
  • Analysis of key histone modifications.
  • Identification and functional validation of Th17-specific enhancers, including one for RORA using CRISPR-Cas9 editing.

Main Results:

  • A set of enhancers controlling Th17 cell fate specification was identified.
  • Twenty-three single nucleotide polymorphisms (SNPs) linked to autoimmune diseases were found within Th17 enhancers, overlapping with transcription factor binding sites.
  • A specific enhancer within the RORA intron was shown to positively regulate RORA transcription, confirmed by CRISPR-Cas9 deletion.

Conclusions:

  • The study reveals critical enhancers governing Th17 cell differentiation.
  • Genetic variants in Th17 enhancers may contribute to autoimmune diseases.
  • The identified RORA enhancer plays a key role in regulating RORA transcription and orchestrating Th17 cell differentiation.