A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in humans

Miguel Casanova (), Madeleine Moscatelli, Louis Édouard Chauvière, Christophe Huret, Julia Samson, Tharvesh Moideen Liyakat Ali, Olga Rosspopoff and Claire Rougeulle ()
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Miguel Casanova: Université de Paris, Epigenetics and Cell Fate, CNRS
Madeleine Moscatelli: Université de Paris, Epigenetics and Cell Fate, CNRS
Louis Édouard Chauvière: Université de Paris, Epigenetics and Cell Fate, CNRS
Christophe Huret: Université de Paris, Epigenetics and Cell Fate, CNRS
Julia Samson: Université de Paris, Epigenetics and Cell Fate, CNRS
Tharvesh Moideen Liyakat Ali: Université de Paris, Epigenetics and Cell Fate, CNRS
Olga Rosspopoff: Université de Paris, Epigenetics and Cell Fate, CNRS
Claire Rougeulle: Université de Paris, Epigenetics and Cell Fate, CNRS

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Transposable elements (TEs) have been proposed to play an important role in driving the expansion of gene regulatory networks during mammalian evolution, notably by contributing to the evolution and function of long non-coding RNAs (lncRNAs). XACT is a primate-specific TE-derived lncRNA that coats active X chromosomes in pluripotent cells and may contribute to species-specific regulation of X-chromosome inactivation. Here we explore how different families of TEs have contributed to shaping the XACT locus and coupling its expression to pluripotency. Through a combination of sequence analysis across primates, transcriptional interference, and genome editing, we identify a critical enhancer for the regulation of the XACT locus that evolved from an ancestral group of mammalian endogenous retroviruses (ERVs), prior to the emergence of XACT. This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways.

Date: 2019
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DOI: 10.1038/s41467-019-13551-1

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