PRAMEL7 and CUL2 decrease NuRD stability to establish ground-state pluripotency
Abstract
Synopsis
Introduction
Results
PRAMEL7-CUL2 and -BC box domains are required for PRAMEL7-CUL2 interaction and UHRF1 degradation
PRAMEL7/CUL2 axis reprograms the developmentally advanced ESC+serum toward ground-state pluripotency gene expression signature
PRAMEL7 affects protein stability of regulators of repressive chromatin states through its interaction with CUL2
PRAMEL7 directly targets factors implicated in the formation of repressive chromatin that are downregulated in a CUL2-dependent manner
PRAMEL7 recruits CUL2 to chromatin
PRAMEL7-CUL2 axis antagonizes the repression of genes associated with NuRD complex
Discussion
Methods
Cell culture
Establishment of ESC lines expressing PRAMEL7
RNA sequencing and data analysis
Principal component analysis
Cell fractionation
Stable isotope labeling by amino acids (SILAC)
Immunoprecipitation
Chromatin-IP
Mass spectrometric analysis
Chromatin immunoprecipitation analysis (ChIP)
ChIPseq data analysis
Data availability
Author contributions
Disclosure and competing interests statement
Acknowledgements
Supporting Information
References
Information & Authors
Information
Published In
This month's cover highlights the article Glucose-derived glutamate drives neuronal terminal differentiation in vitro by Laura D’Andrea, Matteo Audano, Nico Mitro, Elena Marcello, and colleagues. The image shows the mitochondrial network in hippocampal neurons. The Mitochondria Pyruvate Carrier (MPC) is an obligate bottleneck for mitochondrial generation of glutamate required for the terminal differentiation of neurons. Blunting glucose oxidation through MPC inhibition affects glutamate levels, neuronal maturation in terms of morphology and synaptic activity, and impairs local protein synthesis.
Cover illustration conceptualised and created by the authors. Copyright: the authors.
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