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Related Concept Videos

Prokaryotic Transcriptional Activators and Repressors01:58

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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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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 trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
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Operon Model01:23

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The operon model represents a fundamental mechanism of gene regulation in prokaryotes, enabling coordinated expression of genes involved in related metabolic or functional pathways. Operons consist of structural genes, a promoter, and an operator, with transcription regulated by repressors, activators, and small effector molecules.Structure and Function of OperonsAn operon is a cluster of structural genes transcribed together under the control of a single promoter. The promoter region...
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Operons02:09

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Prokaryotes can control gene expression through operons—DNA sequences consisting of regulatory elements and clustered, functionally related protein-coding genes. Operons use a single promoter sequence to initiate transcription of a gene cluster (i.e., a group of structural genes) into a single mRNA molecule. The terminator sequence ends transcription. An operator sequence, located between the promoter and structural genes, prohibits the operon’s transcriptional activity if bound by...
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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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Updated: Aug 22, 2025

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Structure and functional mapping of the KRAB-KAP1 repressor complex.

Guido A Stoll1,2, Ninoslav Pandiloski3, Christopher H Douse3

  • 1Molecular Immunity Unit, Department of Medicine, MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.

The EMBO Journal
|November 7, 2022
PubMed
Summary
This summary is machine-generated.

Researchers elucidated the molecular interaction between KRAB zinc finger proteins (KRAB-ZFPs) and KAP1, revealing a critical interface for controlling transposable elements and maintaining genome stability through epigenetic silencing.

Keywords:
CRISPRiH3K9me3Krüppel-associated boxTransposable elementheterochromatin

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Area of Science:

  • Genetics
  • Molecular Biology
  • Epigenetics

Background:

  • Transposable elements (TEs) are crucial genetic reservoirs but can cause disease if expressed.
  • KRAB domain-containing zinc finger proteins (KRAB-ZFPs) use KAP1/TRIM28 to repress TEs.
  • The precise interaction mechanism between KRAB-ZFPs and KAP1 was previously unknown.

Purpose of the Study:

  • To determine the structural basis of the interaction between KRAB-ZFPs and KAP1.
  • To functionally validate the identified molecular interface.
  • To understand the role of this interaction in epigenetic transcriptional silencing.

Main Methods:

  • X-ray crystallography to determine the structure of KAP1's TRIM domain bound to a ZNF93 KRAB domain.
  • Site-directed mutagenesis to disrupt the KRAB-KAP1 binding interface.
  • Epigenetic transcriptional silencing assays to assess repressive activity.
  • Genome-wide analysis of H3K9me3 deposition.

Main Results:

  • The crystal structure of the KAP1 tripartite motif (TRIM) in complex with the ZNF93 KRAB domain was determined.
  • Structure-guided mutations at the KRAB-KAP1 interface abolished transcriptional repression.
  • Mutations disrupting KRAB binding led to genome-wide loss of H3K9me3 deposition.
  • The identified interface is essential for KAP1 recruitment and epigenetic silencing.

Conclusions:

  • The KRAB-KAP1 molecular interface is structurally defined and functionally critical for transcriptional control.
  • This interaction is central to vertebrate epigenetic regulation and genome stability.
  • The findings enable structure-based optimization of KRABs for CRISPRi applications.