N-Myc and GCN5 Regulate Significantly Overlapping Transcriptional Programs in Neural Stem Cells

Martínez‐Cerdeño, Verónica; Lemen, Jessica M.; Chan, Vanessa; Wey, Alice; Lin, Wenchu; Dent, Sharon Y.R.; Knoepfler, Paul S.

doi:10.1371/journal.pone.0039456

Cited by 57 publications

(50 citation statements)

References 45 publications

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“…Our data are consistent with previous studies that indicated a role for Myc and E2f1 in SAGA complex recruitment to specific target genes in transformed cells (McMahon et al 1998(McMahon et al , 2000Zhang et al 2014). Furthermore, Myc facilitates global maintenance of active acetylated chromatin and recruits Gcn5 to cell cycle-related genes in neural stem cells (Knoepfler et al 2006;Martinez-Cerdeno et al 2012).…”

Section: Discussionsupporting

confidence: 93%

Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

et al. 2015

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Embryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we performed a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identified components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we showed in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that, upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed-forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming.

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Section: Discussionsupporting

confidence: 93%

Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

et al. 2015

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“…This is partly mediated through loss of activation of GCN5 [412]. Also, a conditional mouse Gcn5 knockout in neural stem cells led to large-scale gene expression changes which partially overlapped with those seen in Myc knockouts [413]. Thus, Myc and GCN5 appear to cooperate in a feed-forward loop of activating transcription.…”

Section: Gcn5mentioning

confidence: 93%

The world of protein acetylation

Drazic

Myklebust

Ree

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

659

532

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Acetylation is one of the major post-translational protein modifications in the cell, with manifold effects on the protein level as well as on the metabolome level. The acetyl group, donated by the metabolite acetyl-coenzyme A, can be co- or post-translationally attached to either the α-amino group of the N-terminus of proteins or to the ε-amino group of lysine residues. These reactions are catalyzed by various N-terminal and lysine acetyltransferases. In case of lysine acetylation, the reaction is enzymatically reversible via tightly regulated and metabolism-dependent mechanisms. The interplay between acetylation and deacetylation is crucial for many important cellular processes. In recent years, our understanding of protein acetylation has increased significantly by global proteomics analyses and in depth functional studies. This review gives a general overview of protein acetylation and the respective acetyltransferases, and focuses on the regulation of metabolic processes and physiological consequences that come along with protein acetylation.

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“…A survey of gene expression following a conditional knockout of GCN5 in neural stem cells indicated that one-sixth of the genes affected by loss of GCN5 are also affected in the same manner by loss of MYCN, implicating MYC in histone acetylation at specific promoters (Martinez-Cerdeno et al 2012).…”

Section: The Max Networkmentioning

confidence: 99%

MYC Cofactors: Molecular Switches Controlling Diverse Biological Outcomes

Hann

2014

Cold Spring Harbor Perspectives in Medicine

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The transcription factor MYC has fundamental roles in proliferation, apoptosis, tumorigenesis, and stem cell pluripotency. Over the last 30 years extensive information has been gathered on the numerous cofactors that interact with MYC and the target genes that are regulated by MYC as a means of understanding the molecular mechanisms controlling its diverse roles. Despite significant advances and perhaps because the amount of information learned about MYC is overwhelming, there has been little consensus on the molecular functions of MYC that mediate its critical biological roles. In this perspective, the major MYC cofactors that regulate the various transcriptional activities of MYC, including canonical and noncanonical transactivation and transcriptional repression, will be reviewed and a model of how these transcriptional mechanisms control MYC-mediated proliferation, apoptosis, and tumorigenesis will be presented. The basis of the model is that a variety of cofactors form dynamic MYC transcriptional complexes that can switch the molecular and biological functions of MYC to yield a diverse range of outcomes in a cell-type-and context-dependent fashion.

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N-Myc and GCN5 Regulate Significantly Overlapping Transcriptional Programs in Neural Stem Cells

Cited by 57 publications

References 45 publications

Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming

The world of protein acetylation

MYC Cofactors: Molecular Switches Controlling Diverse Biological Outcomes

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