Similar Datasets
Project description:Determining ELL2 direct targets via ChIPseq
| PRJNA471339 | ENA
Project description:We report RNA-Seq data from MPC11 plasmacytoma cell lines transduced with either control hairpins (shGFP) or hairpins targeting the transcriptional elongation factor ELL2. ELL2 has been identified as regulating the alternative splicing and polyadenylation of immunoglobulin pre-mRNA, and is highly expressed by plasma cells but not other B cells. Notably, ELL2 drives the accumulation of transcripts encoding secreted immunoglobulin at the expense of membrane-associated transcripts. This study sought to examine the impact of ELL2 on mRNA processing at the transcriptome level, and found that ELL2 controls the alternative processing of 12% of annotated transcripts in MPC11 cells. Examination of pre-mRNA splicing patterns in either control or ELL2-depleted cells
2012-09-07 | E-GEOD-40285 | biostudies-arrayexpress
Project description:We report RNA-Seq data from MPC11 plasmacytoma cell lines transduced with either control hairpins (shGFP) or hairpins targeting the transcriptional elongation factor ELL2. ELL2 has been identified as regulating the alternative splicing and polyadenylation of immunoglobulin pre-mRNA, and is highly expressed by plasma cells but not other B cells. Notably, ELL2 drives the accumulation of transcripts encoding secreted immunoglobulin at the expense of membrane-associated transcripts. This study sought to examine the impact of ELL2 on mRNA processing at the transcriptome level, and found that ELL2 controls the alternative processing of 12% of annotated transcripts in MPC11 cells.
2012-09-07 | GSE40285 | GEO
Project description:Processing of Immunoglobulin heavy chain (IgH) mRNA is a paradigm for competition between splicing and polyadenylation. In plasma cells pre-mRNA is polyadenylated mainly at the promoter-proximal secretory site while B-cells utilize a cryptic 5â?? splice site in the last secretory-specific exon; these are mutually exclusive events for all IgH pre-mRNAs. Transcription elongation factor ELL2, more abundant in plasma cells relative to B-cells, was down-modulated by overexpression of heterogenous ribonucleoprotein F, a condition which reduced production of secretory IgH mRNA. Transfection of B-cells with ELL2 and the IgH reporter showed an accelerated use of the secretory poly(A) site, positioned in competition with the splice to M1; a small interfering RNA to ELL2 reduced expression of IgH secretory mRNA. Co-transcription factors ELL1 and PC4 were ineffective at driving secretory-poly(A) site use. ELL2 had little effect on poly(A) site choice with reporters containing tandem-linked poly(A) sites. Shorter forms of ELL2 protein result from both internal initiation at M186 and protein processing. An alternative splicing reporter driven by IgH or non-Ig promoters revealed that ELL2 and its M186 initiated form were able to accelerate exon skipping. Therefore, ELL2 influences IgH pre-mRNA processing through facilitating skipping of the alternative splice to the membrane form. Experiment Overall Design: AxJ plasma cells were stably transfected to overexpress hnRNP-F, -H or empty vector. Clones showing high overexpression levels of F or H by western blot were selected. The IgH sec to mb ratios of these clones were determined. A global gene expression analysis was performed on mRNA from two clones from hnRNP-F, which demonstrated a lower sec:mb ratio, and one from each of the controls: overexpression of hnRNP-H, or transfection with empty vector, or A20 B-cells, using Affymetrix gene micro array technology.
2008-06-18 | E-GEOD-11586 | biostudies-arrayexpress
Project description:To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship.
2018-04-25 | GSE111210 | GEO
Project description:To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship.
2018-04-25 | GSE111199 | GEO
Project description:Processing of Immunoglobulin heavy chain (IgH) mRNA is a paradigm for competition between splicing and polyadenylation. In plasma cells pre-mRNA is polyadenylated mainly at the promoter-proximal secretory site while B-cells utilize a cryptic 5’ splice site in the last secretory-specific exon; these are mutually exclusive events for all IgH pre-mRNAs. Transcription elongation factor ELL2, more abundant in plasma cells relative to B-cells, was down-modulated by overexpression of heterogenous ribonucleoprotein F, a condition which reduced production of secretory IgH mRNA. Transfection of B-cells with ELL2 and the IgH reporter showed an accelerated use of the secretory poly(A) site, positioned in competition with the splice to M1; a small interfering RNA to ELL2 reduced expression of IgH secretory mRNA. Co-transcription factors ELL1 and PC4 were ineffective at driving secretory-poly(A) site use. ELL2 had little effect on poly(A) site choice with reporters containing tandem-linked poly(A) sites. Shorter forms of ELL2 protein result from both internal initiation at M186 and protein processing. An alternative splicing reporter driven by IgH or non-Ig promoters revealed that ELL2 and its M186 initiated form were able to accelerate exon skipping. Therefore, ELL2 influences IgH pre-mRNA processing through facilitating skipping of the alternative splice to the membrane form.
2008-06-01 | GSE11586 | GEO
Project description:The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 rescue]
| PRJNA436170 | ENA
Project description:The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 KO]
| PRJNA436147 | ENA
Project description:Multiple myeloma (MM) is a plasma cell neoplasm that depends on the bone marrow (BM) microenvironment; however, the underlying mechanisms of epigenetic contribution to the pathogenesis of MM are incompletely understood. Here, we delineate the epigenetic-driven transcriptional and splicing program crucial for MM. We recharacterized transcriptional program induced by IL-6/JAK/STAT3 pathway by ChIP-seq and RNA-seq analyses combined with CRIPSR knockout screening database, and identified B cell lineage factors, POU2AF1 and ELL2, as crucial IL-6/JAK/STAT3 targets that are essential for MM cell growth and survival. Genetic depletion of these factors suppressed MM cell growth in vitro and in the xenograft model of IL-6 humanized mice. Mechanistically, POU2AF1 and ELL2 govern MM-distinct transcriptional program representing immaturity, and IL-6/JAK/STAT3 pathway augments this program through upregulating and recruiting these factors to the MM-signature genes. Furthermore, we showed that IL-6 induces alternative splicing that is partly mediated by POU2AF1. Proteomic study identified novel POU2AF1-associated factors that converge in regulation of RNA, including RNA splicing. Indeed, POU2AF1 is adjacent to multiple splicing factors required for MM cell survival and is involved in the organization of nuclear speckles. Finally, we showed that gapmer antisense oligonucleotides (ASOs) targeting POU2AF1 inhibit its expression and MM cell growth in the presence of soluble BM stromal cell factors, including IL-6. Our data demonstrate that IL-6-driven B cell-lineage factors are the vulnerability of MM cells and may represent novel therapeutic targets for this incurable tumor.
2026-02-15 | GSE298692 | GEO