Selective expression of the transcription elongation factor ELL3 in B cells prior to ELL2 drives proliferation and survival
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Cancer Biology Ph.D. Program, University of South Florida, Tampa, FL 33612, United States; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
- Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
- Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
- Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
- Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States. Electronic address: firstname.lastname@example.org.
B cell activation is dependent on a large increase in transcriptional output followed by focused expression on secreted immunoglobulin as the cell transitions to an antibody producing plasma cell. The rapid transcriptional induction is facilitated by the release of poised RNA pol II into productive elongation through assembly of the super elongation complex (SEC). We report that a SEC component, the Eleven -nineteen Lysine-rich leukemia (ELL) family member 3 (ELL3) is dynamically up-regulated in mature and activated human B cells followed by suppression as B cells transition to plasma cells in part mediated by the transcription repressor PRDM1. Burkitt's lymphoma and a sub-set of Diffuse Large B cell lymphoma cell lines abundantly express ELL3. Depletion of ELL3 in the germinal center derived lymphomas results in severe disruption of DNA replication and cell division along with increased DNA damage and cell death. This restricted utilization and survival dependence reveal a key step in B cell activation and indicate a potential therapeutic target against B cell lymphoma's with a germinal center origin.
|Number of pages||9|
|Early online date||31 Aug 2017|
|Publication status||Published - 1 Nov 2017|
- B-Lymphocytes/immunology, Cell Division/genetics, Cell Survival/genetics, DNA Replication/genetics, Gene Expression Regulation/immunology, Humans, Jurkat Cells, RNA Polymerase II/genetics, Transcriptional Elongation Factors/genetics