@article{3e04c28e602640b2b3a2221e310be3d7,
title = "Comparative Epigenomics Reveals that RNA Polymerase II Pausing and Chromatin Domain Organization Control Nematode piRNA Biogenesis",
abstract = "Piwi-interacting RNAs (piRNAs) are important for genome regulation across metazoans, but their biogenesis evolves rapidly. In Caenorhabditis elegans, piRNA loci are clustered within two 3-Mb regions on chromosome IV. Each piRNA locus possesses an upstream motif that recruits RNA polymerase II to produce an ∼28 nt primary transcript. We used comparative epigenomics across nematodes to gain insight into the origin, evolution, and mechanism of nematode piRNA biogenesis. We show that the piRNA upstream motif is derived from core promoter elements controlling snRNA transcription. We describe two alternative modes of piRNA organization in nematodes: in C. elegans and closely related nematodes, piRNAs are clustered within repressive H3K27me3 chromatin, while in other species, typified by Pristionchus pacificus, piRNAs are found within introns of active genes. Additionally, we discover that piRNA production depends on sequence signals associated with RNA polymerase II pausing. We show that pausing signals synergize with chromatin to control piRNA transcription. piRNAs are an important genome regulatory mechanism conserved across metazoans. In the nematode C. elegans, piRNA biogenesis evolved several differences from other metazoans. Beltran et al. study the origin of these differences through an evolutionary approach, discovering that chromatin environment and RNA polymerase II pausing synergize in piRNA biogenesis.",
keywords = "C. elegans, chromatin, comparative epigenomics, epigenetics, evolution, nematodes, piwi-interacting small RNAs",
author = "Toni Beltran and Consuelo Barroso and Birkle, {Timothy Y.} and Lewis Stevens and Schwartz, {Hillel T.} and Sternberg, {Paul W.} and H{\'e}l{\`e}ne Fradin and Kristin Gunsalus and Fabio Piano and Garima Sharma and Chiara Cerrato and Julie Ahringer and Enrique Mart{\'i}nez-P{\'e}rez and Mark Blaxter and Peter Sarkies",
note = "Funding Information: Work in the Sarkies laboratory is funded by a grant from the Medical Research Council MC-A652-5PY80. P.S. was funded by an Imperial College Research Fellowship. L.S. was funded by a Bailie-Gifford PhD studentship. We thank the London Institute of Medical Sciences Genomics Facility for sequencing. Some sequencing was carried out at Edinburgh Genomics, which has core support from the NERC Biomolecular Analysis Facility award UKSBS PR18037. Work in the Mart{\'i}nez-P{\'e}rez laboratory was funded by a grant from the Medical Research Council MC-A652-5PY60. G.S. was funded by a Newton International Fellowship (Royal Society). J.A. was funded by a Wellcome Senior Research Fellowship (101863). T.Y.B. was funded by a Genetics Society Summer Studentship to the Sarkies lab. We thank Christian Eckmann for sharing parn-1 (tm869) mutant worms and Ben Lehner, Matthias Merkenschlager, and Luis Arag{\'o}n for helpful comments on the manuscript. Conceptualization, P.S. M.B. and T.B.; Methodology, T.B. P.S. E.M.P. and M.B.; Investigation, T.B. P.S. C.B. T.Y.B. and L.S.; Formal Analysis, T.B. and P.S.; Resources, J.A. G.S. C.C. H.S. P.W.S. F.P. K.G. and L.S.; Writing – Original Draft, P.S. and T.B.; Writing – Editing, P.S. T.B. M.B. E.M.P. and J.A.; Supervision, P.S. E.M.P. J.A. P.W.S. F.P. K.G. and M.B. The authors declare no competing interests. Funding Information: Work in the Sarkies laboratory is funded by a grant from the Medical Research Council MC-A652-5PY80 . P.S. was funded by an Imperial College Research Fellowship. L.S. was funded by a Bailie-Gifford PhD studentship. We thank the London Institute of Medical Sciences Genomics Facility for sequencing. Some sequencing was carried out at Edinburgh Genomics, which has core support from the NERC Biomolecular Analysis Facility award UKSBS PR18037 . Work in the Mart{\'i}nez-P{\'e}rez laboratory was funded by a grant from the Medical Research Council MC-A652-5PY60 . G.S. was funded by a Newton International Fellowship (Royal Society). J.A. was funded by a Wellcome Senior Research Fellowship (101863). T.Y.B. was funded by a Genetics Society Summer Studentship to the Sarkies lab. We thank Christian Eckmann for sharing parn-1 (tm869) mutant worms and Ben Lehner, Matthias Merkenschlager, and Luis Arag{\'o}n for helpful comments on the manuscript. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = mar,
day = "25",
doi = "10.1016/j.devcel.2018.12.026",
language = "English (US)",
volume = "48",
pages = "793--810.e6",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",
}