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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 Factors02:16

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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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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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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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β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications.

Qian Bian1, Nimish Khanna, Jurgis Alvikas

  • 1Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.

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Nuclear gene targeting relies on specific DNA regions and epigenetic marks. These cis-elements control heterochromatin targeting, influencing gene regulation at the nuclear periphery.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Genomics

Background:

  • Nuclear compartmentalization is crucial for gene regulation.
  • Mechanisms governing gene targeting to specific nuclear locations are not fully understood.

Purpose of the Study:

  • To investigate the cis-regulatory elements and epigenetic requirements for targeting genes to the nuclear periphery.
  • To elucidate how heterochromatin targeting influences gene regulation.

Main Methods:

  • Bacterial artificial chromosome (BAC) transgenesis for autonomous gene targeting.
  • Fluorescent in situ hybridization (FISH) for visualizing DNA localization.
  • ChIP-sequencing and Western blotting to assess histone modifications (H3K9me3, H3K9me2).
  • Knockdown experiments to evaluate the roles of specific methyltransferases (Suv39H, G9a).

Main Results:

  • Three peripheral targeting regions (PTRs) within an HBB BAC were identified, directing targeting towards the nuclear periphery.
  • Peripheral targeting correlated with increased H3K9 trimethylation (H3K9me3) across the β-globin locus.
  • Targeting to heterochromatin compartments was dependent on Suv39H-mediated H3K9me3.
  • Peripheral tethering of the endogenous HBB locus required both Suv39H-mediated H3K9me3 and G9a-mediated H3K9 dimethylation (H3K9me2).

Conclusions:

  • Multiple cis-elements dictate the balance of epigenetic marks and gene positioning within the nucleus.
  • Specific histone methylation patterns are critical for directing genes to distinct heterochromatin compartments and the nuclear periphery.
  • Understanding these mechanisms provides insights into the spatial organization of the genome and its impact on gene regulation.