Proteomics

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DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate the emergence of 2C-like cells and zygotic transcriptional program


ABSTRACT: The molecular mechanism controlling the zygotic genome activation (ZGA) in mammals remains poorly understood. The 2C-like cells spontaneously emerging from cultures of mouse embryonic stem cells (ESCs) share some key transcriptional and epigenetic programs with 2-cell stage embryos. By studying the transition of ESCs into 2C-like cells, we identified Dppa2/4 as important regulators controlling zygotic transcriptional program through directly upregulating the expression of Dux. In addition, we found that DPPA2 protein is sumoylated and its activity is negatively regulated by Sumo E3 ligase PIAS4. PIAS4 is downregulated during zygotic genome activation process and during transitioning of ESCs into 2C-like cells. Depleting Pias4 or overexpressing Dppa2/4 is sufficient to upregulateactivate 2C-like transcriptional program, while depleting Dppa2/4 or forced expression of PIAS4 or Sumo2-Dppa2 inhibits 2C-like transcriptional program. Furthermore, ectopic expression of Pias4 or Sumo2-Dppa2 impairs early mouse embryo development. In summary, our study identifies key molecular rivals consisting of transcription factors and a Sumo2 E3 ligase that regulate the transition of ESCs into 2C-like cells and zygotic transcriptional program upstream of Dux.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Mus musculus  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Yangming Wang  

LAB HEAD: Yangming Wang

PROVIDER: PXD012925 | Pride | 2019-03-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
17-116_YYL0424_BE_NC-1-1.raw Raw
17-116_YYL0424_BE_NC-1-2.raw Raw
17-116_YYL0424_BE_NC-2-1.raw Raw
17-116_YYL0424_BE_NC-2-2.raw Raw
17-116_YYL0424_BE_P4-1-1.raw Raw
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