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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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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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The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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TissueCoCoPUTs: Novel Human Tissue-Specific Codon and Codon-Pair Usage Tables Based on Differential Tissue Gene

Jacob Kames1, Aikaterini Alexaki1, David D Holcomb1

  • 1Division of Plasma Protein Therapeutics, Office of Tissue and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.

Journal of Molecular Biology
|January 27, 2020
PubMed
Summary

We developed TissueCoCoPUTs, a resource detailing tissue-specific codon usage in 51 human tissues. This data reveals unique codon patterns, distinct from genomic distributions, aiding research in translation and genetic diseases.

Keywords:
GTExHomo sapiensgenetic engineeringtRNAtranscriptome

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Protein expression varies significantly across human tissues.
  • Tissue-specific gene expression influences transcriptome codon usage.
  • Genomic codon usage provides a baseline, but tissue-specific factors modify it.

Purpose of the Study:

  • To create a comprehensive computational resource for tissue-specific codon, codon-pair, and dinucleotide usage in Homo sapiens.
  • To analyze unique codon usage patterns across 51 human tissues.
  • To provide a tool for investigating the link between codon usage, tRNA abundance, and translation efficiency.

Main Methods:

  • Utilized transcriptome data from the Genotype-Tissue Expression (GTEx) portal.
  • Compiled tissue-specific codon, codon-pair, and dinucleotide usage data for 51 human tissues.
  • Calculated distances between tissue-specific codon/codon-pair frequencies to generate a dendrogram.

Main Results:

  • Developed the TissueCoCoPUTs database (https://hive.biochemistry.gwu.edu/review/tissue_codon).
  • Identified distinct patterns of codon and codon-pair usage unique to each tissue, differing from the genomic distribution.
  • Generated a dendrogram illustrating relationships based on these unique usage patterns.

Conclusions:

  • The TissueCoCoPUTs resource offers valuable insights into tissue-specific codon usage variations.
  • This resource can help elucidate the relationship between codon usage, tRNA abundance, and translation kinetics.
  • Applications include biotherapeutic development, tissue-specific genetic engineering, and genetic disease prediction.