@article{86a4a730da444ce39befa927a4bb5d4c,
title = "A Role for FACT in RNA Polymerase II Promoter-Proximal Pausing",
abstract = "FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as an activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. In this report, we describe a global analysis of FACT function in Pol II transcription in Drosophila. We present evidence that loss of FACT has a dramatic impact on Pol II elongation-coupled processes including histone H3 lysine 4 (H3K4) and H3K36 methylation, consistent with a role for FACT in coordinating histone modification and chromatin architecture during Pol II transcription. Importantly, we identify a role for FACT in the maintenance of promoter-proximal Pol II pausing, a key step in transcription activation in higher eukaryotes. These findings bring to light a broader role for FACT in the regulation of Pol II transcription. FACT is a histone chaperone implicated in the assembly and disassembly of nucleosomes during transcription. Tettey et al. demonstrate that Drosophila FACT regulates patterns of the transcription-coupled histone marks H3K4me3 and H3K36me3 and helps to maintain promoter-proximal Pol II pausing.",
keywords = "ChIP-nexus, ChIP-seq, FACT, H2A.v, H3K36me3, H3K4me3, PRO-seq, RNA polymerase II, RNA-seq, SSRP1, Spt16, chromatin, promoter-proximal pausing",
author = "Tettey, {Theophilus T.} and Xin Gao and Wanqing Shao and Hua Li and Story, {Benjamin A.} and Chitsazan, {Alex D.} and Glaser, {Robert L.} and Goode, {Zach H.} and Seidel, {Christopher W.} and Conaway, {Ronald C.} and Julia Zeitlinger and Marco Blanchette and Conaway, {Joan W.}",
note = "Funding Information: We thank members of the Stowers Institute Molecular Biology and Tissue Culture Cores for library preparation and next-generation sequencing and for assistance with cell culture, respectively, and Mark Miller for help with the model figure and graphical abstract. This work was supported by funds from the Stowers Institute for Medical Research , United States, and by a grant to the Stowers Institute from the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation , United States. Funding Information: We thank members of the Stowers Institute Molecular Biology and Tissue Culture Cores for library preparation and next-generation sequencing and for assistance with cell culture, respectively, and Mark Miller for help with the model figure and graphical abstract. This work was supported by funds from the Stowers Institute for Medical Research, United States, and by a grant to the Stowers Institute from the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation, United States. T.T.T. M.B. R.C.C. and J.W.C. developed the experimental design; T.T.T. performed most of the experiments; W.S. performed ChIP-nexus and analyzed the data; H.L. and X.G. were the lead analysts; Z.H.G. analyzed RNA-seq; M.B. B.A.S. A.D.C. and C.W.S. performed initial bioinformatic analyses; and R.L.G. provided essential reagents. T.T.T. R.C.C. and J.W.C. wrote the paper, and W.S. and J.Z. edited the paper. R.C.C. J.W.C. M.B. and J.Z. supervised the work. This work was done to fulfill, in part, a requirement for T.T.T.?s PhD thesis research as a student registered with the Open University. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = jun,
day = "25",
doi = "10.1016/j.celrep.2019.05.099",
language = "English (US)",
volume = "27",
pages = "3770--3779.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}