Background: Telomerase up-regulation is found in about 90% of human cancer specimens and contributes actively to carcinogenesis. Results: -Catenin⅐TCF4 plays an important role in telomerase activation. Conclusion: hTERT is a direct transcriptional target of the Wnt/-catenin pathway. Significance: Identifying the function of the Wnt/-catenin pathway in telomerase regulation provides better insight into the role of Wnt pathway in carcinogenesis.
We reveal a set of divergent octamer elements in Drosophila melanogaster (dm) core histone gene promoters. These elements recruit transcription factor POU-domain protein in D. melanogaster 1 (Pdm-1), which along with co-activator dmOct-1 coactivator in S-phase (dmOCA-S), activates transcription from at least the Drosophila histone 2B (dmH2B) and 4 (dmH4) promoters in a fashion similar to the transcription of mammalian histone 2B (H2B) gene activated by octamer binding transcription factor 1 (Oct-1) and Oct-1 coactivator in S-phase (OCA-S). The expression of core histone genes in both kingdoms is coordinated; however, although the expression of mammalian histone genes involves subtype-specific transcription factors and/or co-activator(s), the expression of Drosophila core histone genes is regulated by a common module (Pdm-1/ dmOCA-S) in a directly coordinated manner. Finally, dmOCA-S is recruited to the Drosophila histone locus bodies in the S-phase, marking S-phase-specific transcription activation of core histone genes.Transcription is the foremost critical step for regulating gene activities. Transcription regulation involves interplay among trans-acting activities such as general and gene-specific transcription factors and co-activators in conjunction with RNA polymerase II and cis-acting regulatory elements such as core and proximal promoter elements that are pivotal in recruiting transcription regulators to specify gene expression programs; in turn, changes in transcription (co)factor activities and/or selectivity dictate gene expression outputs, and understanding mechanistic aspects of various gene expression programs often leads to a better understanding of many aspects of physiology (1).We are interested in characterizing the cis-and trans-regulatory networks of the Drosophila core histone genes, which are among the most conserved eukaryotic genes. The conserved DNA replication-dependent canonical histone genes belong to a multigene family, and the encoded proteins (core histones H2A, H2B, H3, and H4 and linker histone H1) are essential components of nucleosomes, the building blocks of metazoan chromatin. Core histone genes of diverse species have clustered features (2). There are two clusters of histone genes in mammalian cells, with the larger cluster (human chromosome 6, mouse chromosome 13) comprising ϳ80% of the genes and the smaller one (human chromosome 1, mouse chromosome 3) containing the remaining (3-5). In Drosophila, multicopied core and linker histone genes are clustered as ϳ5-kb repeats on chromosome 2 (6); Xenopus histone genes are similarly organized (7).Histone biosynthesis occurs almost exclusively in the S-phase (8). For instance, the human H2B (hH2B) 3 gene promoter contains an octamer element (ATTTGCAT) that anchors octamer binding transcription factor 1 (Oct-1), which recruits OCA-S to bring about S-phase-specific H2B expression (9). The transcription of mammalian (core) histone genes is mediated by subtype-specific promoter elements and associated transcription (co)factors (10 -13)...
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