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Global translation during early development depends on the essential transcription factor PRDM10 [RNA-seq]

ABSTRACT: Members of the PR/SET domain-containing (PRDM) family of zinc finger transcriptional regulators play diverse roles in embryonic development and lineage differentiation. PRDM10 is a yet uncharacterized family member, with unknown functions in vivo. Here we report an essential requirement for PRDM10 in the pre-implantation embryo and embryonic stem cells (mESCs), where loss of PRDM10 results in severe cell growth inhibition. Genomic and biochemical analyses reveal that PRDM10 functions as a sequence-specific transcription factor which modulates gene expression by binding to target gene promoters. We identify Eif3b, which encodes a core component of the eukaryotic translation initiation factor 3 (eIF3) complex, as a key downstream target and demonstrate that growth inhibition in PRDM10-deficient mESCs is largely mediated through EIF3B-dependent effects on global translation. This work elucidates the molecular function of PRDM10 in maintaining global translation and establishes its essential role in early embryonic development and mESC homeostasis, offering novel insights into the functional repertoire of PRDMs as well as the transcriptional mechanisms regulating global translation.

ORGANISM(S): Mus musculus

PROVIDER: GSE135021 | GEO | 2020/05/06

REPOSITORIES: GEO

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Global translation during early development depends on the essential transcription factor PRDM10 [RNA-Seq_2]

Project description:Members of the PR/SET domain-containing (PRDM) family of zinc finger transcriptional regulators play diverse roles in embryonic development and lineage differentiation. PRDM10 is a yet uncharacterized family member, with unknown functions in vivo. Here we report an essential requirement for PRDM10 in the pre-implantation embryo and embryonic stem cells (mESCs), where loss of PRDM10 results in severe cell growth inhibition. Genomic and biochemical analyses reveal that PRDM10 functions as a sequence-specific transcription factor which modulates gene expression by binding to target gene promoters. We identify Eif3b, which encodes a core component of the eukaryotic translation initiation factor 3 (eIF3) complex, as a key downstream target and demonstrate that growth inhibition in PRDM10-deficient mESCs is largely mediated through EIF3B-dependent effects on global translation. This work elucidates the molecular function of PRDM10 in maintaining global translation and establishes its essential role in early embryonic development and mESC homeostasis, offering novel insights into the functional repertoire of PRDMs as well as the transcriptional mechanisms regulating global translation.

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EIF3B knockdown

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Controlling tissue patterning by translational regulation of signaling transcripts through the core translation factor eIF3c [I]

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