Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals Export

@article{citeulike:3996534, abstract = {There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts1, 2, 3, 4. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95\%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise5, 6. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95\% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.}, author = {Guttman, Mitchell and Amit, Ido and Garber, Manuel and French, Courtney and Lin, Michael F. and Feldser, David and Huarte, Maite and Zuk, Or and Carey, Bryce W. and Cassady, John P. and Cabili, Moran N. and Jaenisch, Rudolf and Mikkelsen, Tarjei S. and Jacks, Tyler and Hacohen, Nir and Bernstein, Bradley E. and Kellis, Manolis and Regev, Aviv and Rinn, John L. and Lander, Eric S.}, citeulike-article-id = {3996534}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07672}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07672}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19182780}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19182780}, day = {01}, doi = {10.1038/nature07672}, issn = {0028-0836}, journal = {Nature}, keywords = {chromatin, conserved, mammalian, non-protein-coding, rna}, month = {February}, number = {7235}, pages = {223--227}, posted-at = {2009-05-28 09:46:43}, priority = {2}, publisher = {Nature Publishing Group}, title = {Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals}, url = {http://dx.doi.org/10.1038/nature07672}, volume = {458}, year = {2009} }

TY - JOUR ID - citeulike:3996534 L3 - citeulike-article-id:3996534 N2 - There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts1, 2, 3, 4. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise5, 6. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes. IS - 7235 JF - Nature SN - 0028-0836 EP - 227 TI - Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals PB - Nature Publishing Group VL - 458 SP - 223 KW - chromatin KW - conserved KW - mammalian KW - non-protein-coding KW - rna AU - Guttman, Mitchell AU - Amit, Ido AU - Garber, Manuel AU - French, Courtney AU - Lin, Michael AU - Feldser, David AU - Huarte, Maite AU - Zuk, Or AU - Carey, Bryce AU - Cassady, John AU - Cabili, Moran AU - Jaenisch, Rudolf AU - Mikkelsen, Tarjei AU - Jacks, Tyler AU - Hacohen, Nir AU - Bernstein, Bradley AU - Kellis, Manolis AU - Regev, Aviv AU - Rinn, John AU - Lander, Eric PY - 2009/02/01/ UR - http://dx.doi.org/10.1038/nature07672 ER -