Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

AUTS2 confers transcriptional activation to PRC1 in the CNS (ChIP-Seq)

ABSTRACT: Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. ChIP-seq experiments of PRC1 components, PolII as well as histone modifications were performed either in mouse whole brain or in human 293T-REx lines expressing FLAG/HA-tagged subunits. RNA-seq was performed to analyze the expression profile of mouse whole brain.

ORGANISM(S): Mus musculus

SUBMITTER: Zhonghua Gao

PROVIDER: E-GEOD-60409 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

AUTS2 confers transcriptional activation to PRC1 in the CNS (RNA-Seq)

Project description:Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. mRNA profiles of P1 brain from wild type mice were generated by deep sequencing

2014-12-18 | E-GEOD-60410 | biostudies-arrayexpress

AUTS2 confers transcriptional activation to PRC1 in the CNS (RNA-Seq)

2014-12-18 | GSE60410 | GEO

AUTS2 confers transcriptional activation to PRC1 in the CNS (ChIP-Seq)

2014-12-18 | GSE60409 | GEO

WDR68 is essential for the PRC1-AUTS2 complex activating role and for stem cell differentiation

Project description:Recent studies on Polycomb repressive complexes (PRC) reveal a surprising role in transcriptional activation, yet the underlying mechanism remains poorly understood. We previously identified a type 1 PRC (PRC1) that contains Autism Susceptibility Candidate 2 (AUTS2), which positively regulates transcription of neuronal genes. However, the mechanism by which the PRC1-AUTS2 complex influences neurodevelopment is unclear. Here we demonstrate that WDR68 is not only an integral component of the PRC1-AUTS2 complex, it is required for PRC1-AUTS2-mediated transcription activation. Furthermore, deletion of Wdr68 in mouse embryonic stem cells leads to defects in neuronal differentiation without affecting self-renewal. Through transcriptomic analysis, we found that many genes responsible for neuronal differentiation are down-regulated in Wdr68 deficient neural progenitors. These genes include several that are targeted by the PRC1-AUTS2 complex. In summary, our studies uncovered a previously unknown but essential component of the active PRC1 complex and evidence of its role in regulating the expression of genes that may be important for neuronal differentiation.

2020-07-29 | GSE115576 | GEO

AUTS2 confers transcriptional activation to PRC1 in the CNS

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-12-18 | E-GEOD-60411 | biostudies-arrayexpress

ChIP-seq for SCML2 and SCML2 mutants in 293T-REx and K562 cells

Project description:Polycomb repressive complex-1 (PRC1) is essential for the epigenetic regulation of gene expression. SCML2 is a mammalian homolog of Drosophila SCM, a Polycomb-group protein that associates with PRC1. Here, we show that SCML2A, an SCML2 isoform tightly associated to chromatin, contributes to PRC1 localization and also directly enforces repression of certain Polycomb target genes. SCML2A binds to PRC1 via its SPM domain and interacts with ncRNAs through a novel RNA-binding region (RBR). Targeting of SCML2A to chromatin involves the coordinated action of the MBT domains, RNA binding, and interaction with PRC1 through the SPM domain. Deletion of the RBR reduces the occupancy of SCML2A at target genes and overexpression of a mutant SCML2A lacking the RBR causes defects in PRC1 recruitment. These observations point to a role for ncRNAs in regulating SCML2 function and suggest that SCML2 participates in the epigenetic control of transcription directly and in cooperation with PRC1. This is the ChIP-seq part of the study

2014-07-02 | E-GEOD-38273 | biostudies-arrayexpress

Chromatin-associated RNA degradation contributes to silencing of Polycomb target genes

Project description:Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2) are histone-modifying and -binding complexes that mediate the formation of facultative heterochromatin and are required for silencing of developmental genes and maintenance of cell fate. Multiple pathways of RNA decay work together to establish and maintain heterochromatin in fission yeast, including a recently identified role for a conserved RNA degradation complex called the rixosome or RIX1 complex. Whether RNA degradation also plays a role in the stability of mammalian heterochromatin remains unknown. Here we show that the rixosome contributes to silencing of many Polycomb targets in human cells. The rixosome associates with human PRC complexes and is enriched at promoters of Polycomb target genes. Importantly, depletion of either the rixosome or Polycomb results in accumulation of paused and elongating RNA polymerase at Polycomb-target genes. We identify point mutations in the RING1B subunit of PRC1 that disrupt the interaction between PRC1 and the rixosome and result in diminished silencing, suggesting that direct recruitment of the rixosome to chromatin is required for silencing. Finally, we show that the RNA kinase activity of the rixosome and the XRN2 exoribonuclease, which degrades RNAs with 5’ mono-phosphate groups generated by the rixosome, are required for silencing. Our findings suggest that rixosome-mediated degradation of nascent RNA is conserved from fission yeast to human, although in human cells the rixosome degrades RNA in facultative rather than constitutive heterochromatin.

2022-01-20 | PXD029403 | Pride

RIP-seq for SCML2 and SCML2 mutants in 293T-REx and K562 cells

2014-07-02 | E-GEOD-38274 | biostudies-arrayexpress

The Polycomb group protein CBX6 is an essential regulator of embryonic stem cell identity

Project description:Polycomb group proteins are transcriptional repressors that control cell identity and development. In mammals, at least five different CBX proteins are believed to associate with the core Polycomb repressive complex 1 (PRC1). CBX6 and CBX7 are the most highly expressed CBX proteins in embryonic stem cells (ESCs), yet little is known about the function of CBX6 in these cells. Here we show that CBX6 is an essential regulator of ESC identity, since ablation of CBX6 function destabilizes the pluripotency network and triggers differentiation. At the molecular level, CBX6 is linked to the canonical PRC1 (cPRC1) complex; however, contrary to expectations, our results indicate that CBX6 also has a non-canonical PRC1 function. Taken together, our findings reveal that CBX6 is an essential component for ESC biology and contributes to the structural and functional complexity of the PRC1 complex.

2017-09-25 | PXD007577 | Pride

An Auts2-Containing RNA-Binding Complex Regulates Transcript Expression in Developing Cerebral Cortex

Project description:Molecular functions of the intellectual disability syndrome gene AUTS2 remain uncertain. Two mechanisms of Auts2 function have been proposed. One study found that Auts2 modifies Polycomb repressive complex 1 (PRC1) to activate transcription of target neurodevelopmental genes by recruiting EP300, a histone acetyltransferase. A second study found that cytoplasmic AUTS2 regulates cytoskeletal assembly through PREX1 to promote neurite outgrowth and migration. To further investigate Auts2 functions, we screened for AUTS2 interactors in cerebral cortex, and profiled changes of transcript expression in the developing cortex of Auts2 conditional mutant mice. AUTS2 immunoprecipitation experiments identified interactions with proteins involved in pre-mRNA processing, and mRNAs, including those encoding EP300 and PREX1, both bound by AUTS2-containing complexes and dysregulated in Auts2 mutant cortex. We propose that AUTS2 interacts with an RNA-binding complex that directly targets transcripts encoding Auts2 effectors. This mechanism provides a unifying model that accounts for previously disparate hypotheses of AUTS2 functions.

2021-05-21 | GSE112792 | 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