Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase in human, has been identified as the rate-limiting factor in telomerase activity, but its detailed mechanism of transcription regulation remains unclear. In this investigation, a novel human gene telomerase transcriptional elements-interacting factor (TEIF) was isolated from HeLa cell based on hTERT promoter yeast one-hybrid assay. TEIF has a 2358-bp open reading frame encoding a predicted protein of 786 amino acids, which is functionally conserved in general eukaryotic species. The transcription of TEIF was detected in cells and expressed an 86-kDa native protein, distributing mainly in cellular nuclei. Its interaction with hTERT promoter was identified and the DNA binding potential was credited to C-terminus of TEIF. Transfection of TEIF into HeLa cells presented marked transactivation of hTERT promoter and stimulated both endogenous hTERT transcription and telomerase activities. These results suggest that TEIF protein might be a transcription regulator and take part in the activation of hTERT. (C) 2004 Elsevier Inc. All rights reserved.