Cited by 103Telomeres, Telomerase, and SenescenceGenomics and Chromatin DynamicsChromosomal and Genetic Variations

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Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains

Broccoli, D·1997·Human Molecular Genetics

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Abstract

Mammalian chromosome ends contain long arrays of TTAGGG repeats that are complexed to a telomere specific protein, the TTAGGG repeat binding factor, TRF1. Here we describe the characterization of genes encoding the human and mouse TRF1 proteins, hTRF1 and mTRF1. The mTRF1 cDNA was isolated based on sequence similarity to the hTRF1 cDNA and the mTRF1 mRNA was shown to be ubiquitously expressed as a single 1.9 kb polyadenylated transcript in mouse somatic tissues. High levels of a 2.1 kb transcript were found in testes. In vitro translation of the mTRF1 cDNA resulted in a 56 kDa protein that binds to TTAGGG repeat arrays. mTRF1 displayed the same sequence specificity as hTRF1, preferring arrays of TTAGGG repeats as a binding substrate over TTAGGC and TTGGGG repeats. Expression of an epitope-tagged version of mTRF1 showed that the protein is located at the ends of murine metaphase chromosomes. In agreement, conceptual translation indicated that mTRF1 and hTRF1 are similarly-sized proteins with nearly identical C-terminal Myb-related DNA binding motifs. In addition, comparison of the predicted mTRF1 and hTRF1 amino acid sequences showed that the acidic nature of the N-terminus of TRF1 is conserved and revealed a highly conserved novel domain of approximately 200 amino acids in the middle of the proteins. However, other regions of the proteins are poorly conserved (<35% identity) and the overall level of identity of the mTRF1 and hTRF1 amino acid sequences is only 67%. The TRF1 genes are not syntenic; the hTRF1 gene localized to human chromosome 8 band q13 while the mTRF1 gene localized to mouse chromosome 17 band E3. The data indicate that the genes for mammalian telomeric proteins evolve rapidly.

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Authors: Broccoli, D.
Affiliations: Rockefeller University (US)
Corresponding author: Broccoli, D
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 1997-01-01
Volume: 6
Issue: 1
Pages: 69-76
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/6.1.69
OpenAlex: W2113856739
Cited by: 103
References: 46
Citations by year: 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 2 · 2012: 1
FWCI: 4.62
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: National Institutes of Health (5r01ca067021-08)
National Cancer Institute (CA 67021)
National Institute of General Medical Sciences (GM 49046)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: TRF1, telomeres, TTAGGG repeats, human-mouse gene comparison, chromosomal localization, gene expression, conserved domains, sequence evolution, testis-specific gene expression, chromosome ends
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Chromosomes, DNA-Binding Proteins, Genes, Germ Cells, Humans, Metaphase, Molecular Sequence Data, Tissue Distribution, Gene Expression, Open Reading Frames, Telomere, Conserved Sequence, Sequence Homology, Amino Acid, DNA, Complementary, Telomeric Repeat Binding Protein 1, Mice

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Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains

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