Inability to enter S phase and defective RNA polymerase IICTD phosphorylation in mice lacking Mat1

The trimeric Cdk7-cyclin H-Mat1 complex comprises the kinase subunit of bas al transcription factor TFIIH and has been shown to function as a cyclin-de pendent kinase (Cdk)-activating kinase, Herein we report that disruption of the murine Mat1 gene leads to periimplantation lethality coincident with d epletion of maternal Mat1 protein. In culture, Mat1(-/-) blastocysts gave r ise to viable post-mitotic trophoblast giant cells while mitotic lineages f ailed to proliferate and survive. In contrast to wild-type trophoblast gian t cells, Mat1(-/-) cells exhibited a rapid arrest in endoreduplication, whi ch was characterized by an inability to enter S phase. Additionally, Mat1(- /-) cells exhibited defects in phosphorylation of the C-terminal domain (CT D) of RNA polymerase II on both Ser5 and Ser2 of the heptapeptide repeat. D espite this, Mat1(-/-) cells demonstrated apparent transcriptional and tran slational integrity. These data indicate an essential role for Mat1 in prog ression through the endocycle and suggest that while Mat1 modulates CTD pho sphorylation, it does not appear to be essential for RNA polymerase II-medi ated transcription.