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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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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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Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...
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A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
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Structural basis for multiple gene regulation by human DUX4.

Yangyang Li1, Baixing Wu2, Hehua Liu3

  • 1State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200438, China.

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|October 17, 2018
PubMed
Summary
This summary is machine-generated.

Structural studies reveal how the DUX4 double homeodomains (DUX4-DH) bind DNA, crucial for facioscapulohumeral muscular dystrophy and leukemia. Understanding DUX4 DNA recognition advances insights into its role in gene regulation.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • The DUX4 protein is implicated in facioscapulohumeral muscular dystrophy and acute lymphoblastic leukemia.
  • DUX4 functions as a master transcription regulator, activating numerous genes associated with the zygotic genome activation (ZGA).

Purpose of the Study:

  • To elucidate the structural and biochemical basis of DNA recognition by the DUX4 double homeodomains (DUX4-DH).
  • To understand how DUX4 interacts with its target DNA sequences to regulate gene transcription.

Main Methods:

  • X-ray crystallography was used to determine the structures of DUX4-DH bound to DNA.
  • Isothermal Titration Calorimetry (ITC) was employed to assess the binding affinity and thermodynamics of DUX4-DH to various DNA sequences.

Main Results:

  • The structures reveal that both homeodomain 1 (HD1) and homeodomain 2 (HD2) adopt a classical homeobox fold.
  • HD1 and HD2 recognize specific DNA sequences (box1: 5'-TAA-3' and box2: 5'-TGA-3') through interactions in the major and minor grooves.
  • DUX4-DH binding is tolerant to variations in the linker nucleotides and length between the recognized DNA boxes.

Conclusions:

  • These findings provide a structural basis for DUX4's target DNA recognition mechanism.
  • The study enhances the understanding of how DUX4 regulates the transcription of multiple genes, offering insights into its role in disease pathogenesis.