This study introduces a novel approach to identify large non-coding RNAs (lincRNAs) in mammals by leveraging chromatin-state maps. The researchers identified approximately 1,600 multi-exonic lincRNAs across four mouse cell types, which show strong evolutionary conservation and functional significance. These lincRNAs are highly conserved in their genomic loci, exonic sequences, and promoter regions, with over 95% showing clear evolutionary conservation. The study also developed a functional genomics approach to assign putative functions to these lincRNAs, demonstrating their roles in various biological processes such as embryonic stem cell pluripotency and cell proliferation. Independent functional validation was obtained for over 100 lincRNAs using cell-based assays, showing that specific lincRNAs are transcriptionally regulated by key transcription factors. The findings provide a comprehensive collection of highly conserved functional lincRNAs and highlight their diverse biological functions.This study introduces a novel approach to identify large non-coding RNAs (lincRNAs) in mammals by leveraging chromatin-state maps. The researchers identified approximately 1,600 multi-exonic lincRNAs across four mouse cell types, which show strong evolutionary conservation and functional significance. These lincRNAs are highly conserved in their genomic loci, exonic sequences, and promoter regions, with over 95% showing clear evolutionary conservation. The study also developed a functional genomics approach to assign putative functions to these lincRNAs, demonstrating their roles in various biological processes such as embryonic stem cell pluripotency and cell proliferation. Independent functional validation was obtained for over 100 lincRNAs using cell-based assays, showing that specific lincRNAs are transcriptionally regulated by key transcription factors. The findings provide a comprehensive collection of highly conserved functional lincRNAs and highlight their diverse biological functions.