Seitz, Volkhard and Butzhammer, Peter and Hirsch, Burkhard and Hecht, Jochen and Guetgemann, Ines and Ehlers, Anke and Lenze, Dido and Oker, Elisabeth and Sommerfeld, Anke and von der Wall, Edda and Koenig, Christoph and Zinser, Christian and Spang, Rainer and Hummel, Michael (2011) Deep Sequencing of MYC DNA-Binding Sites in Burkitt Lymphoma. PLOS ONE, 6 (11): e26837. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Background: MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far. Methodology/Principal Findings: ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA-mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing. Conclusion/Significance: The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an upregulation of B-cell genes highlight an interesting aspect of BL biology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHIP-CHIP DATA; HUMAN B-CELLS; C-MYC; GENE ANALYSIS; TRANSCRIPTION; TUMORIGENESIS; RECRUITMENT; ACTIVATION; CANCER; IDENTIFICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 May 2020 14:28 |
| Last Modified: | 26 May 2020 14:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19816 |
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