The Eleven-Nineteen Lysine-rich Leukemia Gene (ELL2) Influences the Histone H3 Protein Modifications Accompanying the Shift to Secretory Immunoglobulin Heavy Chain mRNA Production
| Autor: | Kyung Soo Park, Michael Albring, Creityeka Langer, Christine Milcarek |
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| Rok vydání: | 2011 |
| Předmět: |
Transcription
Genetic Polyadenylation Immunoglobulin gamma-Chains Plasma Cells RNA polymerase II Methylation Biochemistry Cell Line Histones Mice Histone H3 hemic and lymphatic diseases Animals Gene Regulation RNA Small Interfering Enhancer Molecular Biology Transcription factor biology RNA 3' Polyadenylation Signals Exons Histone-Lysine N-Methyltransferase Cell Biology Molecular biology Chromatin Histone biology.protein RNA Polymerase II Transcriptional Elongation Factors Chromatin immunoprecipitation Myeloid-Lymphoid Leukemia Protein |
| Zdroj: | Journal of Biological Chemistry. 286:33795-33803 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.272096 |
| Popis: | In plasma cells, immunoglobulin heavy chain (IgH) secretory-specific mRNA is made in high abundance as a result of both increased promoter proximal poly(A) site choice and weak splice-site skipping. Ell2, the eleven-nineteen lysine rich leukemia gene, is a transcription elongation factor that is induced ∼6-fold in plasma cells and has been shown to drive secretory-specific mRNA production. Reducing ELL2 by siRNA, which reduced processing to the secretion-specific poly(A) site, also influenced the methylations of histone H3K4 and H3K79 on the IgH gene and impacted positive transcription factor b (pTEFb), Ser-2 carboxyl-terminal phosphorylation, and polyadenylation factor additions to RNA polymerase II. The multiple lineage leukemia gene (MLL) and Dot1L associations with the IgH gene were also impaired in the absence of ELL2. To investigate the link between histone modifications, transcription elongation, and alternative RNA processing in IgH mRNA production, we performed chromatin immunoprecipitation on cultured mouse B and plasma cells bearing the identical IgH γ2a gene. In the plasma cells, as compared with the B cells, the H3K4 and H3K79 methylations extended farther downstream, past the IgH enhancer to the end of the transcribed region. Thus the downstream H3K4 and H3K79 methylation of the IgH associated chromatin in plasma cells is associated with increased polyadenylation and exon skipping, resulting from the actions of ELL2 transcription elongation factor. |
| Databáze: | OpenAIRE |
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