Trans- and cis-acting effects of the lncRNA; Firre; on epigenetic and structural features of the inactive X chromosome Journal Article uri icon

Overview

abstract

  • Abstract; ; Firre; encodes a lncRNA involved in nuclear organization in mammals. Here we find that; Firre; RNA is transcribed from the active X chromosome (Xa) and exerts trans-acting effects on the inactive X chromosome (Xi). Allelic deletion of; Firre; on the Xa in a mouse hybrid fibroblast cell line results in a dramatic loss of the histone modification H3K27me3 and of components of the PRC2 complex on the Xi as well as the disruption of the perinucleolar location of the Xi. These features are measurably rescued by ectopic expression of a mouse or human; Firre/FIRRE; cDNA transgene, strongly supporting a conserved trans-acting role of the; Firre; transcript in maintaining the Xi heterochromatin environment. Surprisingly, CTCF occupancy is decreased on the Xi upon loss of; Firre; RNA, but is partially recovered by ectopic transgene expression, suggesting a functional link between; Firre; RNA and CTCF in maintenance of epigenetic features and/or location of the Xi. Loss of; Firre; RNA results in dysregulation of genes implicated in cell division and development, but not in reactivation of genes on the Xi, which retains its bipartite structure despite some changes in chromatin contact distribution. Allelic deletion or inversion of; Firre; on the Xi causes localized redistribution of chromatin contacts, apparently dependent on the orientation of CTCF binding sites clustered at the locus. Thus, the; Firre; locus and its RNA have roles in the maintenance of epigenetic features and structure of the Xi.;

publication date

  • June 30, 2019

has restriction

  • closed

Date in CU Experts

  • November 3, 2020 5:00 AM

Full Author List

  • Fang H; Bonora G; Lewandowski JP; Thakur J; Filippova GN; Henikoff S; Shendure J; Duan Z; Rinn JL; Deng X

author count

  • 12

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