A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Kao, Hung Ying; Ordentlich, Peter; Koyano-Nakagawa, Naoko; Tang, Zhenyu; Downes, Michael; Kintner, Chris; Evans, Ronald M.; Kadesch, Tom

doi:10.1101/gad.12.15.2269

Cited by 591 publications

(573 citation statements)

References 35 publications

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“…Based on biochemical experiments, it was proposed that RBP-J can interact directly with TFIID, a general transcription factor [33] or that RBP-J can recruit histone deacetylase-containing complexes. Previously, at least three different interactions between RBP-J and corepressor complexes have been described: a complex containing SMRT/mSin3A/ HDAC-1 (SMRT, Silencing Mediator for Retinoic acid and Thyroid hormone receptor; HDAC-1, histone deacetylase-1) or NCor/mSin3A/HDAC-1 complex [34] and a CIR/SAP30/HDAC-2 complex [35]. So far, the functional relevance of these biochemical findings still remains to be seen.…”

Section: Notch Target Genesmentioning

confidence: 99%

“…Functional interactions between Notch and PCAF and GCN5 have also been observed [47]. Furthermore, histone deacetylases have been implicated in repression mediated by the RBP-J/SHARP corepressor complex [34,48]. There is only very preliminary data available for changes in histone methylation at Notch target genes.…”

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

“…When part of the corepressor complex, SKIP can interact with corepressor SMRT, thereby recruiting histone deacetylases [34]. Hayward and colleagues have presented data that demonstrates SKIP bridges interactions between RBP-J and corepressors or RBP-J and Notch [69,70].…”

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

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The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

584

499

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. The Notch gene encodes a transmembrane receptor that gave the name to the evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Here, we review Notch signaling with a focus on gene regulatory events at Notch target genes. This is of utmost importance to understand Notch signaling since certain RBP-J associated cofactors and particular epigenetic marks determine the specificity of Notch target gene expression in different cell types. We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer.

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Section: Notch Target Genesmentioning

confidence: 99%

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

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The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

584

499

View full text Add to dashboard Cite

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“…The Notch pathway is highly conserved and primarily involved in cell differentiation and tissue development (Kao et al ., 1998). In the liver, Notch signaling is essential in the development of the biliary system as well as regulating transcription factors responsible for hepatoblast differentiation (Valenti et al ., 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear receptor corepressor 2 (NCOR2) is an important regulator of hormone receptor target genes through its interactions with histone deacetylases. Complexes containing NCOR2 and HDAC1 have a transcriptionally repressive influence at Notch target sites (Kao et al ., 1998). Aging is associated with increased expression of Ncor2 in major metabolic tissues, including liver, adipose tissue, and skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition

et al. 2016

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SummaryAdverse environmental exposures of mothers during fetal period predispose offspring to a range of age‐related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers’ nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age‐matched young controls and aged (20‐month‐old) animals. HELP‐tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease.

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Regulation and regulatory parameters of histone modifications

Davie

Chadee

1998

J. Cell. Biochem.

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Histone acetylation and phosphorylation destablizes nucleosome and chromatin structure. Relaxation of the chromatin fiber facilitates transcription. Coactivator complexes with histone acetyltransferase activity are recruited by transcription factors bound to enhancers or promoters. The recruited histone acetyltransferases may acetylate histone or nonhistone chromosomal proteins, resulting in the relaxation of chromatin structure. Alternatively, repressors recruit corepressor complexes with histone deacetylase activity, leading to condensation of chromatin.This review highlights the recent advances made in our understanding of the roles of histone acetyltransferases, histone deacetylases, histone kinases, and protein phosphatases in transcriptional activation and repression. Exciting reports revealing mechanistic connections between histone modifying activities and the RNA polymerase II machinery, the coupling of histone deacetylation and DNA methylation, the possible involvement of histone deacetylases in the organization of nuclear DNA, and the role of chromatin modulators in oncogenesis are discussed. J. Cell. Biochem. Suppls. 30/31:203-213, 1998. © 1998 Wiley-Liss, Inc.

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A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Cited by 591 publications

References 35 publications

The Notch signaling pathway: Transcriptional regulation at Notch target genes

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition

Regulation and regulatory parameters of histone modifications

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