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Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains
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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“Consistent with the poor conservation of TRF1 (9), we have not been able to detect hamster TRF1 with a polyclonal antibody raised against full-length human TRF1 or with a polyclonal antibody raised against a peptide of mouse Trf1.”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [9]
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Control of telomere length by the human telomeric protein TRF1
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Human telomeres contain two distinct Myb–related proteins, TRF1 and TRF2
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Self-citationControl of Human Telomere Length by TRF1 and TRF2
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Telomeric localization of TRF2, a novel human telobox protein
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TRF1 is a dimer and bends telomeric DNA
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Metadata
- 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
- 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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