Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines

被引:50
作者
Doerr, JR
Malone, CS
Fike, FM
Gordon, MS
Soghomonian, SV
Thomas, RK
Tao, Q
Murray, PG
Diehl, V
Teitell, MA
Wall, R [1 ]
机构
[1] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Genet, Los Angeles, CA 90095 USA
[3] Univ Cologne, CMMC, Dept Internal Med 1, D-50924 Cologne, Germany
[4] Chinese Univ Hong Kong, Dept Clin Oncol, Canc Epigenet Lab, Shatin, Hong Kong, Peoples R China
[5] Univ Birmingham, CRUK Inst Canc Studies, Birmingham B15 2TT, W Midlands, England
[6] Univ Calif Los Angeles, Dept Immunol Microbiol, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[9] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
[10] Univ Calif Los Angeles, Inst Cell Mimet Studies, Los Angeles, CA 90095 USA
[11] Univ Calif Los Angeles, Inst Stem Cell Biol & Med, Los Angeles, CA 90095 USA
[12] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
关键词
classical Hodgkin lymphoma; CpG DNA methylation; gene reactivation; gene silencing; primary effusion lymphoma;
D O I
10.1016/j.jmb.2005.05.032
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) and primary effusion lymphoma (PEL) are derived from germinal center (GC) and post-GC B cells, respectively. Neither express many of the B cell genes or surface markers typically expressed by other GC-derived B cell lymphomas or normal B cells. This loss of B cell gene expression is not due to a lack of essential transcription factors, as studies have shown that the ectopic expression of missing transcription factors failed to reactivate endogenous target genes. These results implicate epigenetic mechanisms extinguishing B cell gene expression. Silenced endogenous B cell genes representing a surface receptor, B29 (Ig beta CD79b), a signaling molecule, TCL1, and a transcription factor, Bob1 (OCA-B, OBF-1), were reactivated by 5-aza-2'-deoxycytidine, indicating that gene silencing in HRS and PEL cells is due to DNA methylation. Genomic bisulfite sequencing corroborated this prediction and revealed three distinct patterns of methylation for the silenced B29 and TCL1 promoters. These distinct patterns consisted of 51 promoter CpG methylation alone, 5' and 3' promoter CpG methylation sparing sites in the central cores, and complete CpG methylation throughout the promoter regions. The silenced Bob1 promoter showed one pattern of dense CpG methylation at essentially all sites. These consistent patterns predict that, although gene silencing in many HRS and PEL cells mimics appropriate gene silencing, in some cases of complete CpG methylation throughout entire promoters both the activation and targeting of methylation is abnormal. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:631 / 640
页数:10
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