PT  - JOURNAL ARTICLE
AU  - Li Ding
AU  - Maciej Paszkowski-Rogacz
AU  - Jovan Mircetic
AU  - Debojyoti Chakraborty
AU  - Frank Buchholz
TI  - The Paf1 complex positively regulates enhancer activity in mouse embryonic stem cells
AID  - 10.26508/lsa.202000792
DP  - 2021 Mar 01
TA  - Life Science Alliance
PG  - e202000792
VI  - 4
IP  - 3
4099  - https://www.life-science-alliance.org/content/4/3/e202000792.short
4100  - https://www.life-science-alliance.org/content/4/3/e202000792.full
SO  - Life Sci. Alliance2021 Mar 01; 4
AB  - The RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) plays critical roles in modulating the release of paused RNAPII into productive elongation. However, regulation of Paf1C-mediated promoter-proximal pausing is complex and context dependent. In fact, in cancer cell lines, opposing models of Paf1Cs’ role in RNAPII pause-release control have been proposed. Here, we show that the Paf1C positively regulates enhancer activity in mouse embryonic stem cells. In particular, our analyses reveal extensive Paf1C occupancy and function at super enhancers. Importantly, Paf1C occupancy correlates with the strength of enhancer activity, improving the predictive power to classify enhancers in genomic sequences. Depletion of Paf1C attenuates the expression of genes regulated by targeted enhancers and affects RNAPII Ser2 phosphorylation at the binding sites, suggesting that Paf1C-mediated positive regulation of pluripotency enhancers is crucial to maintain mouse embryonic stem cell self-renewal.