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Kcr proteome in response to p300 KO

ABSTRACT: We used quantitative proteomics to characterize the p300-regulated lysine crotonylome in wild type (WT) and p300 knockout (KO) cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: He Huang

LAB HEAD: Yingming Zhao

PROVIDER: PXD006407 | Pride | 2018-06-26

REPOSITORIES: Pride

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Quantitative Crotonylome Analysis Expands the Roles of p300 in the Regulation of Lysine Crotonylation Pathway.

Huang He H Wang Dan-Li DL Zhao Yingming Y

Proteomics 20180711 15

Lysine crotonylation (Kcr) is a recently identified post-translational modification (PTM) that is regulated by an acetyltransferase, p300. The p300-catalyzed histone Kcr is able to stimulate transcription to a greater degree than the well-studied histone lysine acetylation (Kac). Despite these progresses, the global Kcr substrates regulated by p300 remain largely unknown, hindering efforts to establish mechanistic links between Kcr and p300-mediated phenotypes. Here, a quantitative proteomics st ...[more]

PMID: 29932303

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Transcription profiling of mouse C2AS12 cells infected with (1) wt p300 + tTA, (2) p300deltaTAZ2 +tTA, (3) wt p300 +tTA +doxycycline to define the transcriptional network regulated by ectopic expression of the transcriptional co-activator protein, p300 and define its role in promoting muscle cell survival

Project description:The primary focus of these studies is to define the transcriptional network regulated by ectopic expression of the transcriptional co-activator protein, p300, in order to define its mechanism(s) of action in promoting muscle cell survival. Our laboratory has generated a murine C2-derived myoblast cell line stably expressing an IGF-II cDNA in antisense orientation (C2AS12 cells). These cells proliferate normally in serum-rich growth medium but progressively die in low-serum differentiation medium. Ectopic expression of p300 (a transcriptional co-coactivator with acetyltransferase activity) prevents the progressive cell death induced by serum withdrawal, however, the mechanism of this action is not understood. Further, over-expression of a mutated form of p300, lacking at protein interaction domain (deltaTAZ2), failed to maintain cell viability although it retains catalytic activity. Wild-type and mutant p300 are delivered using recombinant adenoviruses (Ad-p300 and Ad-p300deltaTAZ2) and their expression is regulated by a second recombinant adenovirus encoding the tetracycline transactivator protein (Ad-tTA), affording regulated expression of p300 forms (Tet-off system) and providing a control for viral load. Using these reagents the overall experiment was as follows: Three parallel series of C2AS12 cells were infected with (1) wt p300 + tTA, (2) p300deltaTAZ2 +tTA, (3) wt p300 +tTA +doxycycline. Infected cells were grown to confluence followed by transfer to low-serum differentiation medium (T0). Cell were isolated at this point and following 24 (T24) hours incubation for RNA isolation. Companion dishes of cells were included for analysis by immunocytochemistry to ensure regulated transgene expression and cell viabilities. 6 biological replicates, representing 3 treatment groups, two timepoints and 2 biological outcomes (cell survival with p300wt and apoptotic cell death with p300wt+Dox and p300mut)

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