SRA

Many long non-coding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin, regulation and function of these molecules in individual cell types is poorly understood. We have generated comprehensive catalogs of lncRNA species expressed in human and murine embryonic stem cells (ESCs) and mapped their genomic origin. A surprisingly large fraction of these transcripts (>60%) originate from divergent transcription at promoters of active protein-coding genes. The divergently transcribed lncRNA/mRNA gene pairs exhibit coordinated changes in transcription when ESCs are differentiated into endoderm. A significant number of the divergently transcribed lncRNAs/mRNA pairs are conserved between human and mouse ESCs. Disruption of promoter-associated lncRNA orthologs in a zebrafish model of early development causes gross developmental defects. Our results reveal that transcription of most lncRNA genes is coordinated with transcription of protein-coding genes and that these lncRNAs have roles in early development. Overall design: Analysis of genome-wide lncRNA transcription in human embryonic stem cells and early differentiation using RNA-seq, GRO-seq and ChIP-seq