@article{f14b65423c4643b5b9c9527b0a9a6755,
title = "Complex regulation of Eomes levels mediated through distinct functional features of the Meteor long non-coding RNA locus",
abstract = "Long non-coding RNAs (lncRNAs) are implicated in a plethora of cellular processes, but an in-depth understanding of their functional features or their mechanisms of action is currently lacking. Here we study Meteor, a lncRNA transcribed near the gene encoding EOMES, a pleiotropic transcription factor implicated in various processes throughout development and in adult tissues. Using a wide array of perturbation techniques, we show that transcription elongation through the Meteor locus is required for Eomes activation in mouse embryonic stem cells, with Meteor repression linked to a change in the subpopulation primed to differentiate to the mesoderm lineage. We further demonstrate that a distinct functional feature of the locus—namely, the underlying DNA element—is required for suppressing Eomes expression following neuronal differentiation. Our results demonstrate the complex regulation that can be conferred by a single locus and emphasize the importance of careful selection of perturbation techniques when studying lncRNA loci.",
author = "Noa Gil and Perry, {Rotem Ben-Tov} and Zohar Mukamel and Alex Tuck and Marc B{\"u}hler and Igor Ulitsky",
note = "We thank the Weizmann Institute Stem Cells facility for assistance with generating the Meteor pEX and pAS cell lines. We thank Yonatan Stelzer and Phillip Grote for helpful discussions and members of the Ulitsky lab for helpful discussions and comments on the manuscript. We thank Amos Tanay and members of the Tanay lab for discussions on 4C and on analysis of scRNA-seq and Eyal David for discussions on analysis of 3′ RNA-seq. We thank Jacob Hanna, Nofar Mor, and members of the Hanna lab, as well as Yossi Buganim and Mufeed Abdeen, for discussions on mESC growth conditions. We thank Liat Fellus Alyagor and Dana Hirsch for their help with single-molecule fluorescence in situ hybridization experiments. This study was supported by grants to I.U. from the European Research Council Consolidator grant program (lncIMPACT project) and from the Helen and Martin Kimmel Institute for Stem Cell Research. Z.M. is the incumbent of the anonymous Europe Endowment for Research Fellow Chair in artificial intelligence, and R.B.-T.P. is the incumbent of the Arlyn Imberman Research Fellow Chair. Author contributions - N.G. and I.U. conceived the study. N.G. and R.B.-T.P. carried out experiments. N.G. analyzed all high-throughput data. Z.M. assisted with generating scRNA-seq libraries. A.T. and M.B. generated the Meteor fKO and Rz-KD model. N.G. and I.U. wrote the manuscript with input from the other authors.",
year = "2023",
month = jun,
day = "27",
doi = "10.1016/j.celrep.2023.112569",
language = "الإنجليزيّة",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}