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The little elongation complex (LEC) regulates small nuclear RNA transcription

ABSTRACT: The Eleven-nineteen Lysine-rich Leukemia (ELL)-containing Super Elongation Complex (SEC) containing P-TEFb is a key regulator in the expression of HOX genes in Mixed Lineage Leukemia (MLL)-based leukemia. We have identified an SEC-like complex in Drosophila, as well as a distinct ELL-containing complex that lacks P-TEFb and other components of SEC named the "little elongation complex" (LEC). LEC subunits are highly enriched at RNA Polymerase II (Pol II) transcribed small nuclear RNA (snRNA) genes and the loss of LEC results in decreased snRNA expression in both flies and mammals. The discovery of specificity of SEC and LEC complexes for mRNA and snRNA containing genes, respectively, suggest the presence of specific classes of elongation factors for each class of genes transcribed by RNA polymerase II.

ORGANISM(S): Mus musculus Drosophila melanogaster

PROVIDER: GSE32120 | GEO | 2011/12/22

SECONDARY ACCESSION(S): PRJNA147449

REPOSITORIES: GEO

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The little elongation complex (LEC) regulates small nuclear RNA transcription

Project description:The Eleven-nineteen Lysine-rich Leukemia (ELL)-containing Super Elongation Complex (SEC) containing P-TEFb is a key regulator in the expression of HOX genes in Mixed Lineage Leukemia (MLL)-based leukemia. We have identified an SEC-like complex in Drosophila, as well as a distinct ELL-containing complex that lacks P-TEFb and other components of SEC named the "little elongation complex" (LEC). LEC subunits are highly enriched at RNA Polymerase II (Pol II) transcribed small nuclear RNA (snRNA) genes and the loss of LEC results in decreased snRNA expression in both flies and mammals. The discovery of specificity of SEC and LEC complexes for mRNA and snRNA containing genes, respectively, suggest the presence of specific classes of elongation factors for each class of genes transcribed by RNA polymerase II. Examination of genome-wide binding profiles for ELL, Ice1, Lilli, and Pol II in D. melanogaster and by ChIP-seq. Identification of differentially expressed genes in ELL-RNAi and Ice1-RNAi in D. melanogaster by RNA-seq. Examination of genome-wide binding profiles for ELL in M. musculus. Identification of differentially expressed genes in ELL-RNAi in M. musculus by RNA-seq.

2011-12-22 | E-GEOD-32120 | biostudies-arrayexpress

The role of Mediator and Little Elongation Complex in transcription termination

Project description:Mediator is a coregulatory complex involved in regulating the transcription of Pol II-dependent genes. Metazoan Mediator subunit MED26 functions as a docking site for the ELL/EAF-containing Super Elongation Complex (SEC) and L ittle Elongation Complex (LEC), which regulate the expression of distinct genes. MED26 helps to recruit SEC to protein-coding genes including c-Myc and LEC to small nuclear RNA (snRNA) genes. However, why MED26 takes advantage of SEC or LEC to regulate different claases of genes is unclear. Here, we present evidence that MED26 recruits LEC to support optimal transcription termination at non-polyadenylated genes including snRNA and replication-dependent histone (RDH) genes. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and then LEC promotes 3’-end processing through the recruitment of Integrator or Heat labile factor to snRNA or RDH genes, respectively.

2020-01-21 | GSE121024 | GEO

Schizosaccharomyces pombe Pol II Transcription Elongation Factor ELL Functions as Part of a Rudimentary Super Elongation Complex

Project description:ELL family transcription factors activate the overall rate of RNA polymerase II (Pol II) transcription elongation by binding directly to Pol II and suppressing its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation as part of a large multisubunit complex referred to as the Super Elongation Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family protein. Although orthologs of ELL and EAF have been identified in lower eukaryotes including S. pombe, it has been unclear whether SEC-like complexes function in lower eukaryotes. In this report, we describe isolation from S. pombe of an ELL-containing complex with features of a rudimentary SEC. This complex includes S. pombe Ell1, Eaf1, and a previously uncharacterized protein we designate Ell1 binding protein 1 (Ebp1), which is distantly related to metazoan AFF family members. Like the metazoan SEC, this S. pombe ELL complex appears to function broadly in Pol II transcription. Interestingly, it appears to have a particularly important role in regulating genes involved in cell separation.

2018-07-26 | GSE115636 | GEO

Multiple roles for LEC in initiation and elongation phases of snRNA gene transcription

Project description:The small nuclear RNA (snRNA) genes have been widely used as a model system for understanding transcriptional regulation due to unique aspects of their promoter structure, selectivity for either RNA Polymerase (Pol) II or III and a unique mechanism of termination that is tightly linked with the promoter. Recently, we identified the Little Elongation Complex (LEC) in Drosophila that is required for the expression of Pol II-transcribed snRNA genes. Here, we identify the molecular mechanism by which LEC specifically regulates Pol II-dependent snRNA gene transcription. We present genetic and molecular evidence from both Drosophila and mammals that LEC regulates both initiation and elongation stages of transcription of Pol II-transcribed snRNA genes. In human HCT116 cells we performed: ChIP-seq of ICE1, ICE2, ZC3H8, ELL, and AFF4; total RNA-seq following ICE1 knock-down and non-targeting (GFP) knock-down; ChIP-seq of ICE1 and Pol II following non-targetting (shGFP) and ICE1 knock-down (shICE1). In fly S2 cells we performed: Ice1 ChIP-seq following small hairpin knock-down of GFP (shGFP/non-targeting control) and Ice1 (knock-down of Ice1); ChIP-seq of Pol II following small hairpin knock-down of GFP (shGFP/non-targeting control), Ice1 (knock-down of Ice1), and Ell (knock-down of Ell).

2013-08-08 | E-GEOD-47938 | biostudies-arrayexpress

Gene expression Microarray analysis for HEK293 WT and ELL KD with control and 1hr EGF stimulated conditions.

Project description:Transcription is a multi-stage process that coordinates several steps within the transcription cycle including chromatin reorganization, RNA polymerase II recruitment, initiation, promoter clearance and elongation. Recent advances have identified the super elongation complex (SEC), containing the eleven nineteen lysine rich leukemia protein (ELL), as a key regulator of transcriptional elongation. We show here that ELL plays a diverse and kinetically distinct role prior to its assembly into the SEC by stabilizing Pol II recruitment/initiation and entry into the pause site. Loss of ELL destabilizes the PIC complexes and results in disruption of early elongation and promoter proximal chromatin structure prior to recruitment of AFF4 and other SEC components. These changes result in significantly reduced transcriptional activation of rapidly induced genes. Thus, ELL plays an early and essential role during rapid high amplitude gene expression that is required for both Pol II pause site entry and release.

2011-12-09 | GSE34104 | GEO

Gene expression Microarray analysis for HEK293 WT and ELL KD with control and 1hr EGF stimulated conditions.

2011-12-09 | E-GEOD-34104 | biostudies-arrayexpress

Super Elongation Complex (SEC) and global genomic analyses in murine embryonic stem (ES) cells and in human cells in response to activation signals.

Project description:Transcriptional regulation of developmentally controlled genes is at the heart of differentiation and organogenesis. In this study, we have performed global genomic analyses in murine embryonic stem (ES) cells and in human cells in response to activation signals. We have identified an essential role for the ELL/P-TEFbcontaining Super Elongation Complex (SEC) in the regulation of gene expression including several genes bearing paused RNA polymerase II (Pol II). Paused Pol II has been proposed to be associated with loci that respond rapidly to environmental stimuli. However, our studies in ES cells have also identified a requirement for SEC at genes without preloaded Pol II, which also respond dynamically to differentiation signals. Our findings suggest that SEC is a major class of active P-TEFb-containing complexes required for transcriptional activation in response to environmental cues such as differentiation signals. Examination of ELL2, AFF4, and Pol II before and after activation signals in two cell types.

2011-07-19 | E-GEOD-30267 | biostudies-arrayexpress

Super Elongation Complex (SEC) and global genomic analyses in murine embryonic stem (ES) cells and in human cells in response to activation signals.

2011-07-19 | GSE30267 | GEO

The SEC family of RNA Polymerase II elongation factors: gene target specificity and transcriptional output

Project description:The elongation stage of transcription is a highly regulated in metazoan. We previously purified the AFF1/AFF4-containing Super Elongation Complex (SEC) as a major regulator of development and cancer pathogenesis. Here, we report the biochemical isolation of SEC-like 2 (SEC-L2) and SEC-like 3 (SEC-L3) containing AFF2 and AFF3 in association with P-TEFb, ENL, and AF9. The SEC family members demonstrate high levels of Pol II CTD kinase activity, however, only SEC is required for the proper induction of the HSP70 gene upon stress. Genome-wide mRNA-seq analyses demonstrate that SEC-L2-3 control the expression of different subsets of genes, while AFF4/SEC plays a more dominant role in rapid gene expression in cells. MYC is one of the direct targets of AFF4/SEC, and the SEC requirement to the MYC gene regulates its expression in different cancer cells bearing either acute myeloid or lymphoid leukemia. These findings suggest that AFF4/SEC could be a potential therapeutic target for the treatment of leukemia or other cancers associated with MYC overexpression.

2012-05-02 | GSE34097 | GEO

The SEC family of RNA Polymerase II elongation factors: gene target specificity and transcriptional output

2012-05-01 | E-GEOD-34097 | biostudies-arrayexpress

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