ELL2 Transcription Elongation Factor Regulates Secretory-Specific mRNA Production in Plasma Cells

Researchers from the University of Pittsburgh have identified a crucial role for the eleven-nineteen lysine-rich leukemia gene (ELL2) in regulating secretory-specific mRNA production in plasma cells. According to the study, published in the Journal of Biological Chemistry, ELL2 is induced sixfold in plasma cells and drives the production of secretory-specific mRNA by promoting the processing of transcription and the addition of polyadenylation factors to RNA polymerase II. The researchers also found that reducing ELL2 expression impairs histone modifications, transcription factor binding, and alternative RNA processing, leading to reduced production of secretory-specific mRNA.

Key Takeaways:

  • ELL2 transcription elongation factor is induced sixfold in plasma cells and drives secretory-specific mRNA production.
  • Reducing ELL2 expression impairs histone modifications, including H3K4 and H3K79 methylation, on the IgH gene.
  • ELL2 influences the binding of positive transcription factor b (pTEFb) and polyadenylation factor additions to RNA polymerase II.
  • The multiple lineage leukemia gene (MLL) and Dot1L associations with the IgH gene were impaired in the absence of ELL2.
  • Chromatin immunoprecipitation studies showed that H3K4 and H3K79 methylation extends farther downstream in plasma cells compared to B cells.

Statistics:

  • ELL2 expression is induced sixfold in plasma cells.
  • The H3K4 and H3K79 methylation marks extend farther downstream in plasma cells (past the IgH enhancer to the end of the transcribed region).
  • The study used chromatin immunoprecipitation on cultured mouse B and plasma cells to investigate the link between histone modifications, transcription elongation, and alternative RNA processing.

Sources:

  • C. Milcarek and colleagues, University of Pittsburgh, School Medical, Dept. of Immunology, Pittsburgh, PA 15261, United States.
  • Journal of Biological Chemistry, vol. 286, no. 39 (2011), pp. 33795-33803.
  • American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA.