RT Journal Article
SR Electronic
T1 Splicing of enhancer-associated lincRNAs contributes to enhancer activity
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000663
DO 10.26508/lsa.202000663
VO 3
IS 4
A1 Jennifer Y Tan
A1 Adriano Biasini
A1 Robert S Young
A1 Ana C Marques
YR 2020
UL https://www.life-science-alliance.org/content/3/4/e202000663.abstract
AB Transcription is common at active mammalian enhancers sometimes giving rise to stable enhancer-associated long intergenic noncoding RNAs (elincRNAs). Expression of elincRNA is associated with changes in neighboring gene product abundance and local chromosomal topology, suggesting that transcription at these loci contributes to gene expression regulation in cis. Despite the lack of evidence supporting sequence-dependent functions for most elincRNAs, splicing of these transcripts is unexpectedly common. Whether elincRNA splicing is a mere consequence of cognate enhancer activity or if it directly impacts enhancer function remains unresolved. Here, we investigate the association between elincRNA splicing and enhancer activity in mouse embryonic stem cells. We show that multi-exonic elincRNAs are enriched at conserved enhancers, and the efficient processing of elincRNAs is strongly associated with their cognate enhancer activity. This association is supported by their enrichment in enhancer-specific chromatin signatures; elevated binding of co-transcriptional regulators; increased local intra-chromosomal DNA contacts; and strengthened cis-regulation on target gene expression. Our results support the role of efficient RNA processing of enhancer-associated transcripts to cognate enhancer activity.