P-TEFb, the Super Elongation Complex and Mediator Regulate a Subset of Non-paused Genes during Early Embryo Development


Embryo development involves formation of various cell types through the regulation of gene transcription, resulting in expression of cell type specific RNAs and proteins. A key regulatory step in transcription of animal genes involves the transition of RNA polymerase II (Pol II) into active elongation. At many genes, Pol II is transiently paused approximately 50 basepairs downstream of the transcription start site. Release from this promoter-proximal pausing involves the kinase P-TEFb, which phosphorylates negative elongation factors, allowing Pol II to enter into productive elongation. In this work, we have depleted a considerable amount of P-TEFb from early Drosophila embryos. We find that several genes with paused Pol II can be expressed relatively normally in P-TEFb depleted embryos, whereas expression of some non-paused genes is substantially reduced. This result suggests that also non-paused genes transit through a P-TEFb-dependent checkpoint before entering active elongation. Unexpectedly, we find less Pol II associated with these non-paused genes in P-TEFb embryos. We demonstrate that a protein complex involved in recruitment of Pol II to promoters, the Mediator complex, show the same morphological and gene expression phenotypes as P-TEFb. We propose that Mediator and P-TEFb function together in recruiting Pol II to a subset of developmental genes.


Vyšlo v časopise: P-TEFb, the Super Elongation Complex and Mediator Regulate a Subset of Non-paused Genes during Early Embryo Development. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004971
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004971

Souhrn

Embryo development involves formation of various cell types through the regulation of gene transcription, resulting in expression of cell type specific RNAs and proteins. A key regulatory step in transcription of animal genes involves the transition of RNA polymerase II (Pol II) into active elongation. At many genes, Pol II is transiently paused approximately 50 basepairs downstream of the transcription start site. Release from this promoter-proximal pausing involves the kinase P-TEFb, which phosphorylates negative elongation factors, allowing Pol II to enter into productive elongation. In this work, we have depleted a considerable amount of P-TEFb from early Drosophila embryos. We find that several genes with paused Pol II can be expressed relatively normally in P-TEFb depleted embryos, whereas expression of some non-paused genes is substantially reduced. This result suggests that also non-paused genes transit through a P-TEFb-dependent checkpoint before entering active elongation. Unexpectedly, we find less Pol II associated with these non-paused genes in P-TEFb embryos. We demonstrate that a protein complex involved in recruitment of Pol II to promoters, the Mediator complex, show the same morphological and gene expression phenotypes as P-TEFb. We propose that Mediator and P-TEFb function together in recruiting Pol II to a subset of developmental genes.


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