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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

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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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Transcription Initiation01:47

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Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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Cooperative Binding of Transcription Regulators02:13

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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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Transcription Factors02:16

Transcription Factors

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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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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Related Experiment Video

Updated: Jul 24, 2025

High-throughput Purification of Affinity-tagged Recombinant Proteins
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Structural insights into human TFIIIC promoter recognition.

Wolfram Seifert-Davila1,2, Mathias Girbig1, Luis Hauptmann1

  • 1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.

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Summary

This study reveals the structural mechanism of transcription factor IIIC (TFIIIC) binding to transfer RNA (tRNA) genes. Understanding TFIIIC

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

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • Transcription factor (TF) IIIC is essential for recruiting RNA polymerase (Pol) III to target genes.
  • The recognition of intragenic A- and B-box motifs in transfer RNA (tRNA) genes by TFIIIC modules τA and τB is crucial for tRNA synthesis but mechanistically unclear.

Purpose of the Study:

  • To elucidate the structural mechanism of TFIIIC binding to tRNA genes.
  • To understand how TFIIIC recognizes DNA motifs and initiates transcription.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structures of human TFIIIC.
  • Structures were obtained for both unbound TFIIIC and TFIIIC bound to a tRNA gene.

Main Results:

  • The τB module recognizes the B-box through DNA shape and sequence readout involving multiple winged-helix domains.
  • TFIIIC220 acts as a linker between the τA and τB modules via a flexible ~550-amino acid residue region.
  • High-affinity B-box recognition anchors TFIIIC to DNA, facilitating A-box scanning and TFIIIB recruitment for Pol III activation.

Conclusions:

  • The study provides a detailed structural mechanism for TFIIIC-DNA interaction in tRNA gene transcription.
  • This work clarifies how TFIIIC binding initiates the assembly of the transcription pre-initiation complex for Pol III.
  • The findings offer insights into the regulation of tRNA synthesis at a molecular level.