Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of Mediator and Little Elongation Complex in transcription termination

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121024 | GEO | 2020/01/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The 3' Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies’ association with histone locus bodies

Project description:The non-polyadenylated mRNAs of replication-dependent histones (RDHs) and small nuclear RNAs (snRNAs) are synthesized by RNA polymerase II at histone locus bodies (HLBs) and Cajal bodies (CBs), respectively. We previously showed that MED26-containing Mediator regulates the 3'-end processing of non-polyadenylated transcripts by recruiting Little Elongation Complex (LEC) to the genes. HLBs frequently associate with CBs, in which 3'-end processing factors for RDH genes are enriched; however, this association’s role has not been elucidated. Here, we show that disruption of the Mediator docking site for LEC by mutating the MED26-binding site of EAF1, a subunit of LEC, interferes with CBs’ association with HLBs, resulting in decreased inter-chromosome interaction between RDH gene clusters and increased aberrant unprocessed RDH gene transcripts. Our findings suggest a model in which LEC recruitment by Mediator plays a role in CBs’ association with HLBs to facilitate the 3'-end processing of RDH genes by supplying 3'-end processing factors.

2022-04-26 | GSE164144 | GEO

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 little elongation complex (LEC) regulates small nuclear RNA transcription

2011-12-22 | GSE32120 | GEO

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

2013-08-08 | GSE47938 | 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

Identification of Med26 target genes in Human HEK 293T cells

Project description:Med26 is a subunit of the Human Mediator complex. The Mediator complex is an evolutionarily conserved coregulatory complex that interacts with RNA polymerase II to regulate gene expression. In metazoa, Mediator is composed of some 30 distinct subunits. Mediator exists in multiple, functionally distinct forms that share a common core of subunits and can be distinguished by the presence or absence of a kinase module composed of Med12, Med13, Cdk8, and Cyclin C. In higher eukaryotes, a subset of Mediator complexes is associated with an additional subunit, Med26. This Med26-containing Mediator copurifies from cells with little or no kinase module, but near-stoichiometric Pol II. Evidence suggests that Med26-containing Mediator plays a key role in transcriptional activation however, the mechanism(s) by which Med26 contributes to this process are not known. To identify Med26 target genes, we used Affymetrix U133A plus 2.0 expression arrays to analyze mRNA expression in 293T cells from which Med26 had been depleted by transient transfection by each of three different siRNAs. Three different independent Med26 siRNA knockdowns were compared to a non-targeting control in triplicate, for a total of 12 samples.

2011-08-31 | E-GEOD-28715 | biostudies-arrayexpress

Identification of Med26 target genes in Human HEK 293T cells

2011-09-01 | GSE28715 | GEO

Distinct roles of the two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA Pol II transcription elongation [RNA-seq 2]

Project description:The P-TEFb-containing super elongation complex (SEC) plays the essential role in transcriptional elongation control. The AF4/FMR2 family members AFF1 and AFF4 are the central scaffold proteins of SEC, associated with different human diseases. However, their specific roles in transcriptional control remain unclear. Here, we report that AFF1 and AFF4 show distinct genomic distribution patterns around TSS. AFF1 binds upstream of TSS, while AFF4 is enriched downstream of TSS. Pol II occupancies are reduced genome-widely after depletion of AFF1, but not AFF4. Interestingly, in a subset of active genes with broad AFF4 binding signature, AFF4 disruption causes slow elongation and early termination, while AFF1 deletion mirrors the transcriptional defects observed in the fast Pol II mutant. Furthermore, AFF4 knockdown leads to increased AFF1 levels at chromatin, and vice versa. In summary, our data demonstrate that AFF1 and AFF4 function, to some extent, antagonistically to ensure proper Pol II transcription.

2023-07-02 | GSE224754 | GEO

Distinct roles of the two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA Pol II transcription elongation [ChiP-seq 3]

2023-07-02 | GSE224753 | GEO

Distinct roles of the two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA Pol II transcription elongation [ChIP-seq 1]

2023-07-02 | GSE207320 | GEO