A component of the ARC/Mediator complex required for TGFβ/Nodal signalling

Kato, Yoichi; Habas, Raymond; Katsuyama, Yu; Näär, Anders M.; He, Xi

doi:10.1038/nature00969

Cited by 149 publications

(121 citation statements)

References 30 publications

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“…For instance, Med1 (also known as Trap220) is required for nuclear receptor proliferator-activated receptor ␥2-stimulated adipogenesis but is dispensable for MyoD-mediated myogenesis (35). Likewise, Med15 (also known as Arc-105) is required for TGF-␤͞Nodal signaling but not for BMP͞Smad1 signaling (36), and Med23 (also known as Sur2) is selectively required for transcription factors activated in MAP kinase pathways (37). Therefore, Mot͞Med12 may exert its selective effects by interacting with spatially and temporally distinct transcription factors.…”

Section: Discussionmentioning

confidence: 99%

A subunit of the mediator complex regulates vertebrate neuronal development

Wang

Yang

Uno

et al. 2006

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

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The unique profiles of gene expression dictate distinct cellular identity. How these profiles are established during development is not clear. Here we report that the mutant motionless (mot), identified in a genetic screen for mutations that affect neuronal development in zebrafish, displays deficits of monoaminergic neurons and cranial sensory ganglia, whereas expression of the panneuronal marker Hu is largely unperturbed; GABAergic and subsets of cranial motor neurons do not appear to be deficient. Positional cloning reveals that mot encodes Med12, a component of the evolutionarily conserved Mediator complex, whose in vivo function is not well understood in vertebrates. mot͞med12 transcripts are enriched in the embryonic brain and appear distinct from two other Mediator components Med17 and Med21. Delivery of human med12 RNA into zebrafish restores normality to the mot mutant and, strikingly, leads to premature neuronal differentiation and an increased production of monoaminergic neuronal subtypes in WT. Further investigation reveals that mot͞med12 is necessary to regulate, and when overexpressed is capable of increasing, the expression of distinct neuronal determination genes, including zash1a and lim1, and serves as an in vivo cofactor for Sox9 in this process. Together, our analyses reveal a regulatory role of Mot͞ Med12 in vertebrate neuronal development. D uring vertebrate development, pluripotent stem cells respond to spatially localized signals that regulate their cell cycle exit and subsequent differentiation into specialized cell types. The central nervous system contains a large number of different cell types and has been an organ of interest for studying progenitor cell commitment͞differentiation and the generation of cellular diversity (1, 2). In addition to spatial control, temporal regulation of neuronal development has been appreciated but is much less understood in the vertebrate nervous system (3, 4). It is widely accepted that progenitor cells need to establish unique profiles of gene expression that dictate their final destiny. Intracellular pathways underlying the establishment of precise gene expression patterns in the developing nervous system are not well understood.We have undertaken a genetic approach to characterize genes and pathways that control vertebrate neuronal development by using zebrafish as a model system (5-8). Here, we describe the molecular characterization of the motionless (mot) mutant isolated from our genetic screen. The mot mutant embryos have defects in movement and neuronal and cardiovascular development (9). Current analyses reveal that they have normal brain patterning and do not suffer a global deficit of neurons as evidenced by largely unperturbed expression of the pan-neuronal marker Hu. However, the mot mutant exhibits deficits in neuronal subtypes that include monoaminergic (MA) neurons [forebrain dopaminergic and serotonergic (5HT) neurons, hindbrain noradrenergic (NA) and 5HT neurons, and neural-crest derived sympathetic neurons] and cranial sensory gangli...

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Section: Discussionmentioning

confidence: 99%

A subunit of the mediator complex regulates vertebrate neuronal development

Wang

Yang

Uno

et al. 2006

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

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“…Another MDT-15 ortholog, Xenopus laevis XARC105, induces neural and mesendodermal genes specifically in response to activin/TGF-␤ signaling (Kato et al 2002). As the Smad/TGF-␤ pathway is well conserved in C. elegans, MDT-15 may therefore participate in TGF-␤ signal transduction in C. elegans.…”

Section: Mdt-15 May Participate In Multiple Signal Transduction Cascadesmentioning

confidence: 99%

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans

Taubert¹,

Gilst²,

Hansen³

et al. 2006

Genes Dev.

234

312

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“…As well as being able to recruit HATs to chromatin, the SMADs can bind Mediator components. A direct interaction between SMAD2 and the Mediator component ARC105 (activator-recruited cofactor 105), and ARC105 was shown to be important for SMAD2-mediated transcription in Xenopus embryos (Kato et al 2002).…”

Section: Smad Interactions With Coactivators and Corepressors Lead Tomentioning

confidence: 99%

Transcriptional Control by the SMADs

Hill

2016

Cold Spring Harb Perspect Biol

289

256

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The transforming growth factor-b (TGF-b) family of ligands elicit their biological effects by initiating new programs of gene expression. The best understood signal transducers for these ligands are the SMADs, which essentially act as transcription factors that are activated in the cytoplasm and then accumulate in the nucleus in response to ligand induction where they bind to enhancer/promoter sequences in the regulatory regions of target genes to either activate or repress transcription. This review focuses on the mechanisms whereby the SMADs achieve this and the functional implications. The SMAD complexes have weak affinity for DNA and limited specificity and, thus, they cooperate with other site-specific transcription factors that act either to actively recruit the SMAD complexes or to stabilize their DNA binding. In some situations, these cooperating transcription factors function to integrate the signals from TGF-b family ligands with environmental cues or with information about cell lineage. Activated SMAD complexes regulate transcription via remodeling of the chromatin template. Consistent with this, they recruit a variety of coactivators and corepressors to the chromatin, which either directly or indirectly modify histones and/or modulate chromatin structure.

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A component of the ARC/Mediator complex required for TGFβ/Nodal signalling

Cited by 149 publications

References 30 publications

A subunit of the mediator complex regulates vertebrate neuronal development

A subunit of the mediator complex regulates vertebrate neuronal development

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans

Transcriptional Control by the SMADs

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