RBP-Jκ/SHARP Recruits CtIP/CtBP Corepressors To Silence Notch Target Genes

Oswald, Franz; Winkler, Michael; Cao, Ying; Astrahantseff, Kathy; Bourteele, Soizic; Knöchel, Walter; Borggrefe, Tilman

doi:10.1128/mcb.25.23.10379-10390.2005

Cited by 160 publications

(161 citation statements)

References 42 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…So far, the functional relevance of these biochemical findings still remains to be seen. We recently characterized an RBP-associated repressor complex composed of corepressors RBP-J, SHARP (SMRT and HDAC associated repressor protein), CtBP (C-terminal binding protein) and CtIP (CtBP interacting protein) [36]. The relevance of this finding is supported by genetic data in Drosophila where RBP-J homologue Su(H) can recruit the corepressor dCtBP [37,38].…”

Section: Notch Target Genesmentioning

confidence: 96%

“…SHARP contains RRMs (RNA Recognition Motifs) in the amino-terminal region and a highly conserved SPOC-domain at the very C-terminus [76] and reviewed in [77]; this domain has been crystallized and contains a highly conserved positively charged patch which is crucial for the interaction with corepressors SMRT/NCoR [78,79]. The very last 34 amino acids of the SPOC-domain of SHARP are required for binding to corepressors CtIP/CtBP [36] and ETO (Eight-twenty-one) (Fig. 1) [78,79].…”

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

“…It is intriguing that, CtIP, ETO and SMRT bind to the same small region of the large 400kDa protein SHARP. In the absence of NICD, the RBP-J/SHARP heterodimer recruits corepressors CtIP/CtBP to Notch target genes [36], (Fig. 1A).…”

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

See 2 more Smart Citations

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

564

469

View full text Add to dashboard Cite

Section: Notch Target Genesmentioning

confidence: 96%

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

See 1 more Smart Citation

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

564

469

View full text Add to dashboard Cite

“…Rbpsuh is a DNA-binding regulator that activates Notch pathway target genes upon Notch signaling. However, in the absence of signaling, it serves as a transcriptional repressor through recruitment of the CtBP corepressor complex (21). In ESC the expression of all ligands and receptors in this pathway are very low, but both Rbpsuh and Ctbp2 are highly expressed in ESC and down-regulated but still expressed upon differentiation (SI Fig.…”

Section: Cis-regulatory Analysis Of Genes Repressed In Escmentioning

confidence: 99%

A gene regulatory network in mouse embryonic stem cells

Zhou

Chipperfield²,

Melton³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

249

247

View full text Add to dashboard Cite

We analyze new and existing expression and transcription factorbinding data to characterize gene regulatory relations in mouse ES cells (ESC). In addition to confirming the key roles of Oct4, Sox2, and Nanog, our analysis identifies several genes, such as Esrrb, Stat3, Tcf7, Sall4, and LRH-1, as statistically significant coregulators. The regulatory interactions among 15 core regulators are used to construct a gene regulatory network in ESC. The network encapsulates extensive cross-regulations among the core regulators, highlights how they may control epigenetic processes, and reveals the surprising roles of nuclear receptors. Our analysis also provides information on the regulation of a large number of putative target genes of the network.cis-regulatory module ͉ transcriptional regulation R ecent research has established the fundamental roles of several transcription factors (TF), namely Oct4, Sox2, and Nanog, in the self-renewal and pluripotency of mouse ES cells (ESC) (reviewed in ref. 1). In addition to these three ''master regulators,'' a large number of additional TF have been implicated to play a role in ESC biology, including Stat3, Esrrb, Tbx3, Foxd3, LRH-1, Klf4, Myc, P53, and Sall4 (2-8). The emerging picture is that these TF regulate each other and interact with epigenetic control factors to form a large gene regulatory network in ESC. However, the regulatory interactions within this network have not been worked out. Here, we analyze new and published gene expression and location (ChIP-chip/ChIP-PET) data sets to reconstruct a part of this network computationally. We identify collaborating TF that may work with the master regulators to activate gene expression in ESC, as well as collaborating factors that may play a repressive role. Our analyses also predict the cis-regulatory sequences (down to the location of binding sites) that mediate the combinatorial control of these TF on their target genes. Results Genes Correlated or Affected by Oct4Expression. Several lines of evidence point to Oct4 as one of the most important regulators in ESC. Null mutants of Oct4 are not viable and fail to form a functional inner cell mass (9). A twofold increase or decrease of Oct4 levels leads to differentiation into primitive endoderm/ mesoderm or trophectoderm, respectively (10). ESC show a very dramatic change in gene expression when subject to RNAi knockdown of Oct4, as compared with RNAi knockdowns of other essential regulators (3). Moreover, Oct4 is one of the four regulators that together can reprogram fibroblast cells to pluripotent cells with ESC-like morphology (6). No other ESC regulator shares these properties. Because a transcriptional target is likely to have expression correlated with its regulator, the first step in our analysis was to identify genes whose expression strongly correlates with that of Oct4. To do this, we used an ES line harboring a GFP reporter driven by the Oct4 distal enhancer (11). FACS based on this reporter allowed the purification of subpopulations of cells according to their Oct4...

show abstract

“…In the nucleus, NICD forms a complex with the DNA-binding protein Rbp-J, and the coactivator Mastermind [12,13 ], recruiting histone acetyltransferases, and other cofactors required for transcriptional activation [14][15][16]. In the absence of Notch activation, Rbp-J represses target gene expression by interacting with corepressors including SMRT, SHARP, CtBP, and histone deacetylases [17][18][19][20]. The most well characterized Notch signaling targets include members of the Hairy enhancer of split (Hes) family Hes1, Hes5, and the Hes-related protein (Herp) family (review in [21]).…”

Section: Temporally Regulated Notch Signaling Is Required For Sequentmentioning

confidence: 99%

Signaling and epigenetic regulation of pituitary development

Zhu

Wang

et al. 2007

Current Opinion in Cell Biology

View full text Add to dashboard Cite

The developing pituitary gland provides an instructive model system for elucidating the molecular mechanisms by which distinct cell types arise from a common progenitor lineage accompanied by changes in the chromatin status in response to multiple extrinsic and intrinsic signals. Recent studies have shed light on the integration between signaling molecules and activation of transcription factors that are essential for cell fate commitment and terminal differentiation. Investigation of the in vivo function of the histone modifying enzyme LSD1 has revealed a new layer of regulatory mechanism in pituitary organogenesis. Epigenetic studies of the transcriptional events in terminal differentiation process have provided insights into the functions of non-coding RNA and developmentally regulated chromatin organization.

show abstract

RBP-Jκ/SHARP Recruits CtIP/CtBP Corepressors To Silence Notch Target Genes

Cited by 160 publications

References 42 publications

The Notch signaling pathway: Transcriptional regulation at Notch target genes

The Notch signaling pathway: Transcriptional regulation at Notch target genes

A gene regulatory network in mouse embryonic stem cells

Signaling and epigenetic regulation of pituitary development

Contact Info

Product

Resources

About