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TY - JOUR AU - Czudnochowski, Nadine AU - Bösken, Christian A. AU - Geyer, Matthias PY - 2012 DA - 2012/05/15 TI - Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition JO - Nature Communications SP - 842 VL - 3 IS - 1 AB - Phosphorylation of RNA polymerase II carboxy-terminal domain (CTD) in hepta-repeats YSPTSPS regulates eukaryotic transcription. Whereas Ser5 is phosphorylated in the initiation phase, Ser2 phosphorylation marks the elongation state. Here we show that the positive transcription elongation factor P-TEFb is a Ser5 CTD kinase that is unable to create Ser2/Ser5 double phosphorylations, while it exhibits fourfold higher activity on a CTD substrate pre-phosphorylated at Ser7 compared with the consensus hepta-repeat or the YSPTSPK variant. Mass spectrometry reveals an equal number of phosphorylations to the number of hepta-repeats provided, yet the mechanism of phosphorylation is distributive despite the repetitive nature of the substrate. Inhibition of P-TEFb activity is mediated by two regions in Hexim1 that act synergistically on Cdk9 and Cyclin T1. HIV-1 Tat/TAR abrogates Hexim1 inhibition to stimulate transcription of viral genes but does not change the substrate specificity. Together, these results provide insight into the multifaceted pattern of CTD phosphorylation. SN - 2041-1723 UR - https://doi.org/10.1038/ncomms1846 DO - 10.1038/ncomms1846 ID - Czudnochowski2012 ER -