TCL1 is activated by chromosomal rearrangement or by hypomethylation

Yuille, Martin; Condie, Alison; Stone, Elaine M.; Wilsher, Julie; Bradshaw, Paul S.; Brooks, Lucy; Catovsky, Daniel

doi:10.1002/gcc.1099

Cited by 69 publications

(45 citation statements)

References 20 publications

(21 reference statements)

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“…Site Determination-A transcription initiation site has been suggested at 41 bp downstream of a putative TATA box based upon the initial reverse transcriptase-PCR cloning of the TCL1 cDNA (1,15). However, the TCL1 start site has not been experimentally determined, and this position would be inconsistent with known start sites from TATA box-dependent promoters, which are generally 25-30 nucleotides downstream of the first T in the TATA sequence (reviewed in Refs.…”

Section: Tcl1 Transcriptional Startmentioning

confidence: 99%

“…1) (47). Based on differential sensitivity at a single NotI restriction enzyme site in this core promoter, Yuille et al (15) previously concluded that TCL1 silencing was mediated by CpG methylation. Their finding that TCL1 expression was activated in silenced cells by 5-AC treatment was advanced as further support for this conclusion, although this reactivation experiment does not distinguish between direct and indirect effects resulting from 5-AC treatment.…”

Section: Tcl1 Transactivation By Sp1mentioning

confidence: 99%

“…The TCL1 promoter and other potential regulatory regions have not been characterized, and there have been no reports of 14q32.1 rearrangements with associated dysregulation of TCL1 for B-cell malignancies, including TCL1-expressing Burkitt lymphomas (BL), B-chronic lymphocytic leukemias (␤-CLL), or DLBCL (15). Initial studies by Yuille et al (15) reported a correlation between the methylation status of two CpG sites within a single NotI site in the putative TCL1 promoter and TCL1 expression levels.…”

mentioning

confidence: 99%

“…Initial studies by Yuille et al (15) reported a correlation between the methylation status of two CpG sites within a single NotI site in the putative TCL1 promoter and TCL1 expression levels. Also, treatment of TCL1 non-expressing Jurkat and CEM T-cells with the DNA methyltransferase inhibitor 5-aza-2Ј-deoxycytidine (5-AC) was reported to activate TCL1 expression, suggesting a potential role for epigenetic modifications in TCL1 gene silencing (15). While providing important first clues, further analyses are needed to improve our understanding of the mech-anisms regulating TCL1 in expressing and silent cell types during development and in cancer.…”

mentioning

confidence: 99%

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Sp1 Transactivation of the TCL1 Oncogene

French¹,

Malone²,

Shen³

et al. 2003

Journal of Biological Chemistry

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Cis-regions and trans-factors controlling TCL1 oncogene expression are not known. We identified the functional TCL1 promoter by mapping four transcriptional start sites 24 -30 bp downstream of a TATA box. A 424-bp fragment upstream of the major start site showed robust promoter activity comparable with SV40 in both TCL1 expressing and non-expressing cell lines. Additional constructs spanning 10 kb upstream and 20 kb downstream of the start site showed only modest increases in reporter activity indicating that TCL1 expression is primarily controlled by the promoter. Ten putative Sp1-binding sites were identified within 300 bp of the start site, and three of these specifically bound Sp1. A dosedependent transactivation of the TCL1 promoter with Sp1 addition in Sp1-negative Drosophila SL2 cells was observed, and mutation of the three identified Sp1-binding sites significantly repressed reporter gene expression in 293T cells, confirming a key role for Sp1 in activating the TCL1 promoter in vivo. In TCL1 silent cell lines, CpG DNA methylation was rarely observed at functional Sp1 sites, and methylation of a previously reported NotI restriction site was associated with dense CpG methylation rather than endogenous TCL1 gene silencing. Together, these results indicate that Sp1 mediates transactivation of the TCL1 core promoter and that TCL1 gene silencing is not dependent on mechanisms involving Sp1 and NotI site methylation.

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Section: Tcl1 Transcriptional Startmentioning

confidence: 99%

Section: Tcl1 Transactivation By Sp1mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Sp1 Transactivation of the TCL1 Oncogene

French¹,

Malone²,

Shen³

et al. 2003

Journal of Biological Chemistry

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“…The promoter region of the TCL-1 gene contains methylated CpG sequences in mature (IgM ϩ ) B cells and in acute T cell leukemia lines (26). We have tested the methylation status of five CpG sites at and around the NotI site of the TCl-1 promoter by pyrosequencing the bisulfite-treated genomic DNA.…”

Section: Tcl-1 Expression Inmentioning

confidence: 99%

T cell leukemia I oncogene expression depends on the presence of Epstein–Barr virus in the virus- carrying Burkitt lymphoma lines

Kiss

Nishikawa

Takada

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Molecular Basis of Mature T-Cell Leukemia

Pekarsky

Hallas²,

Croce³

2001

JAMA

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T-cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) is a lymphoproliferative disease derived from immunocompetent post-thymic T cells. Activation (initiation of expression) of the TCL1 locus at chromosome 14q32.1 appears to be the causal event in the pathogenesis of these mature T-cell leukemias. This activation occurs as a result of translocations or inversions that cause rearrangement of the TCL1 (T-cell leukemia/lymphoma 1) locus with regulatory elements of T-cell receptor genes. To describe the molecular events that take part in the leukemogenesis of mature T-cell leukemias, we reviewed the literature and our own data on the molecular basis of mature T-cell leukemia. This data search revealed that 4 genes have been identified at the TCL1 locus: TCL1, TCL1b, TNG1, and TNG2. The expression of these genes is substantially increased following rearrangements involving 14q32.1. Functional analysis of the Tcl1 protein revealed its involvement in an Akt (protein kinase B) prosurvival pathway through its interaction with the Akt kinase, which promotes translocation of Akt to the nucleus and increases Akt's enzymatic activity. The available data provide important insights into the molecular mechanisms of T-cell leukemogenesis that may lead to the development of new drugs for treatment of mature T-cell leukemia.

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TCL1 is activated by chromosomal rearrangement or by hypomethylation

Cited by 69 publications

References 20 publications

Sp1 Transactivation of the TCL1 Oncogene

Sp1 Transactivation of the TCL1 Oncogene

T cell leukemia I oncogene expression depends on the presence of Epstein–Barr virus in the virus- carrying Burkitt lymphoma lines

Molecular Basis of Mature T-Cell Leukemia

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