Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224753 | GEO | 2023/07/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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 | GSE207812 | GEO

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

2023-07-02 | GSE207810 | 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

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

2023-07-02 | GSE224754 | GEO

Gene target specificity of the Super Elongation Complex (SEC) family: How HIV-1 Tat employs selected SEC members to activate viral transcription

Project description:The AF4/FMR2 proteins AFF1 and AFF4 act as a scaffold to assemble the Super Elongation Complex (SEC) that strongly activates transcriptional elongation of HIV-1 and cellular genes. Although they can dimerize, it is unclear whether the dimers exist and function within a SEC in vivo. Furthermore, it is unknown whether AFF1 and AFF4 function similarly in mediating SEC-dependent activation of diverse genes. Providing answers to these questions, our current study shows that AFF1 and AFF4 reside in separate SECs that display largely distinct gene target specificities. While the AFF1-SEC is more potent in supporting HIV-1 transactivation by the viral Tat protein, the AFF4-SEC is more important for HSP70 induction upon heat shock. The functional difference between AFF1 and AFF4 in Tat-transactivation has been traced to a single amino acid variation between the two proteins, which causes them to enhance the affinity of Tat for P-TEFb, a key SEC component, with different efficiency. Finally, genome-wide analysis confirms that the genes regulated by AFF1- and AFF4-SEC are largely non-overlapping and perform distinct functions. Thus, the SEC represents a family of related complexes that exist to increase the regulatory diversity and gene control options during transactivation of diverse cellular and viral genes. RNA-seq in HeLa cells of wild-type and after RNAi of AFF1 or AFF4.

2015-05-20 | E-GEOD-69021 | biostudies-arrayexpress

Gene target specificity of the Super Elongation Complex (SEC) family: How HIV-1 Tat employs selected SEC members to activate viral transcription

2015-05-20 | GSE69021 | GEO

AFF4 globally affects the release of paused RNA polymerase II in HEL cells [ChIP-seq]

Project description:P-TEFb, a heterodimer of kinase, CDK9, and Cyclin T1, is a critical regulator of promoter-proximal pause release of Pol II in metazoans. It is capable of forming three larger multiprotein complexes, including the super elongation complex (SEC), the BRD4/P-TEFb complex and the 7SK snRNP. In the SEC or the BRD4/P-TEFb, P-TEFb is enzymatically active, while in the 7SK snRNP, its activity is inhibited. The SEC consists of AFF1 or 4, ENL or AF9, ELL1, 2 or 3 and EAF1 or 2 in addition to P-TEFb, the only subunit with catalytic activity, and the noncatalytic subunits have been found to be able to regulate pause release through P-TEFb. One recent study showed that in human DLD-1 cells, the SEC only regulates pause release of heat shock (HS) genes, whereas the BRD4/P-TEFb complex regulates pause release of the rest of the genes. In this study, we found that AFF4 knockdown in human HEL cells decreased not only cellular level but also global chromatin occupancy of CTD serine 2 phosphorylated Pol II, and notably, increased promoter-proximal pause of Pol II on several hundred HS and thousands of non-HS genes. Mechanistically, AFF4 facilitates pause release likely by facilitating the binding of P-TEFb to Pol II. These results suggest that the extent of impact of AFF4 on pause release is likely to be context-dependent or cell-type dependent.

2024-06-10 | GSE235444 | GEO

AFF4 globally affects the release of paused RNA polymerase II in HEL cells [PRO-seq]

2024-06-10 | GSE234619 | GEO

AFF4 globally affects the release of paused RNA polymerase II in HEL cells [RNA-seq]

2024-06-10 | GSE234617 | GEO

AFF1-HEXIM1 cooperation suppresses rapid-response differentiation initiators to enforce epidermal progenitor maintenance

Project description:In this study we identified an essential role of the SEC, a crucial regulator of Pol II dynamics, in repressing differentiation for epidermal progenitor maintenance. This repression of differentiation is specifically mediated by the scaffold protein AFF1, but not AFF4. Mechanistically, we find that AFF1-SEC associates with the HEXIM1-containing inactive-PTEFb to directly repress a group of rapid-response genes, which feature robust Pol II pausing near their promoters in the progenitor state. De-repression of these genes occurs within 3 hours of SEC-PTEFb disruption by the peptidomimetic inhibitors. These rapid-response genes include the transcription factor ATF3. Increased ATF3 level is sufficient to promote the expression of key differentiation activators, such as PRDM1, OVOL1, GRHL3 and ZNF750. Furthermore, we find that the dissociation of inactivate P-TEFb from SEC mediates the earliest events of PKC signaling, in triggering epidermal differentiation.

2022-06-24 | GSE182959 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data