A cluster of polypyrimidine tracts is involved in the transcription regulation of telomerase transcriptional elements-interacting factor.
In a previous study, we demonstrated that telomerase transcriptional elements-interacting factor (TEIF) could up-regulate the expression of telomerase and DNA polymerase beta, increasing resistance to genotoxic agents. Here, we further report that TEIF can be stimulated by DNA damage and we have identified a cluster of repeated polypyrimidine tracts in the promoter of TEIF, which mediate both its basal transcription and its response to genotoxic agents. These polypyrimidine tracts are arranged in three types of repeating units and in each of these units there are 14 bp length tandem sequences, which are repeated three times. These sequences are also characteristically separated by an 11 bp interval sequence. Among these units, one type (5'-CCCCCCCATCCCCG-3') has been found to be involved in the transcriptional regulation of TEIF. At the same time, PTB1 (polypyrimidine tract-binding protein 1) has been shown to repress TEIF expression through interaction with this element. Up-regulation of TEIF may be achieved by PTB1 suppression that is induced by DNA damage, or by an olignucleotide decoy, which mediates reversal of suppression. This study provides new insight into the mechanism through which TEIF is involved in DNA damage response, together with insight into the role of polypyrimidine tracts in transcription regulation.
Sun
Ying
Y
Department of Pathology, Health Science Center of Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Sun
Qian
Q
McNutt
Michael A
MA
Gong
Yilei
Y
Wang
Jiaochen
J
Hou
Lin
L
Shen
Qi
Q
Ling
Yun
Y
Chi
Yingkai
Y
Zhang
Bo
B
D033942:Adaptor Proteins, Vesicular Transport; D001483:Base Sequence; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011743:Pyrimidines / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014162:Transfection
D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D011743:Pyrimidines; C464929:SCYL1 protein, human; D014157:Transcription Factors; D038941:Polypyrimidine Tract-Binding Protein