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Related Concept Videos

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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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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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The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
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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: Sep 23, 2025

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
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APOBEC3A regulates transcription from interferon-stimulated response elements.

Manabu Taura1,2, John A Frank1, Takehiro Takahashi1

  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.

Proceedings of the National Academy of Sciences of the United States of America
|May 13, 2022
PubMed
Summary

APOBEC3A (A3A) protein binds TTTC motifs near genes, suppressing interferon-stimulated gene expression. Loss of A3A increases antiviral responses, revealing its role in a negative feedback loop.

Keywords:
A3AHIVISGISRELTR

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Area of Science:

  • Molecular Biology
  • Immunology
  • Virology

Background:

  • APOBEC3A (A3A) is a cytidine deaminase known to inhibit viral replication.
  • A3A also suppresses HIV-1 transcription independently of its deaminase activity.
  • The broader role of A3A in regulating host gene expression remained largely unexplored.

Purpose of the Study:

  • To investigate whether A3A targets host genomic loci for gene repression.
  • To determine the DNA motif recognized by A3A for binding.
  • To elucidate A3A's role in interferon-stimulated gene (ISG) regulation.

Main Methods:

  • Genome-wide motif analysis to identify A3A binding sites.
  • Analysis of TTTC doublet and motif occurrences in gene promoters.
  • Experimental validation using ISG15 expression assays.
  • RNA-sequencing to assess global gene expression changes upon A3A loss.

Main Results:

  • A3A binds to TTTC motifs, which are enriched in promoters of antiviral and type I interferon (IFN-I) signaling genes.
  • A3A binding to Interferon-Stimulated Response Elements (ISRE) inhibits STAT-1 phosphorylation.
  • A3A loss leads to increased IFN-I-dependent induction of ISGs, including ISG15.

Conclusions:

  • APOBEC3A (A3A) plays an unexpected role in regulating interferon-stimulated genes.
  • A3A functions as a repressor of ISGs by binding to TTTC motifs within ISREs.
  • A3A contributes to a negative feedback loop in the type I interferon signaling pathway.