Comparison of the Human and Mouse Genes Encoding the Telomeric Protein, TRF1: Chromosomal Localization, Expression and Conserved Protein Domains

Author： Broccoli Dominique Chong Laura Oelmann Stefan Fernald Anthony A. Marziliano Nicola van Steensel Bas Kipling David Le Beau Michelle M. de Lange Titia

Publisher： Oxford University Press

ISSN： 1460-2083

Source： Human Molecular Genetics, Vol.6, Iss.1, 1997-01, pp. : 69-76

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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 ∼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="" bande3.="" the="" data="" indicate="" that="" the="" genes="" for="" mammalian="" telomeric="" proteins="" evolve="" rapidly.="">