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

Guttman, Mitchell; Amit, Ido; Garber, Manuel; French, Courtney; Lin, Michael; Feldser, David M.; Huarte, Maite; Zuk, Or; Carey, Bryce W.; Cassady, John P.; Cabili, Moran N.; Jaenisch, Rudolf; Mikkelsen, Tarjei S.; Jacks, Tyler; Hacohen, Nir; Bernstein, B; Kellis, M; Regev, Aviv; Rinn, John L.; Lander, Eric S.

doi:10.1038/nature07672

Cited by 3,701 publications

(3,691 citation statements)

References 30 publications

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“…Athough the promoters of lncRNAs are mostly well conserved (Johnsson et al, 2014, Derrien et al, 2012, Pang et al, 2006, these lncRNA transcripts tend to be less well conserved than other protein-coding transcripts (Guttman et al, 2009, Ponjavic et al, 2007. Nonetheless, they are largely functionally conserved (Johnsson et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

McKiernan

Molloy

Cryan

et al. 2014

The International Journal of Biochemistry & Cell Biology

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

McKiernan

Molloy

Cryan

et al. 2014

The International Journal of Biochemistry & Cell Biology

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“…''HIF-1a target genes'' indicate genes with expression levels that were induced more than twofold by hypoxia b The number of HIF-1a target TSCs corresponding to alternative promoters (APs) which had been characterized as RefSeq transcript variants (first column) and those which were newly identified in this study (second column). The numbers of corresponding genes are shown in parentheses c The number of HIF-1a target TSCs located in intergenic regions overlap against the previously reported repertoire of putatively-functional long non-coding RNAs (Guttman et al 2009). We considered that these intergenic TSCs were not derived from our experimental errors, especially those identified in DLD-1 cells (Barski et al 2007;Welboren et al 2009), since we detected clear binding signals for pol II around 61 (21%) and 2 (2%) intergenic TSC targets of HIF-1a.…”

Section: Hif-1a Binding Sites In Intergenic Regionsmentioning

confidence: 95%

Genome-wide identification and annotation of HIF-1α binding sites in two cell lines using massively parallel sequencing

Tanimoto

Tsuchihara

Kanai

et al. 2010

HUGO J

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We identified 531 and 616 putative HIF-1a target sites by ChIP-Seq in the cancerous cell line DLD-1 and the non-cancerous cell line TIG-3, respectively. We also examined the positions and expression levels of transcriptional start sites (TSSs) in these cell lines using our TSS-Seq method. We observed that 121 and 48 genes in DLD-1 and TIG-3 cells, respectively, had HIF-1a binding sites in proximal regions of the previously reported TSSs that were up-regulated at the transcriptional level. In addition, 193 and 123 of the HIF-1a target sites, respectively, were located in proximal regions of previously uncharacterized TSSs, namely, TSSs of putative alternative promoters of protein-coding genes or promoters of putative non-protein-coding transcripts. The hypoxic response of DLD-1 cells was more significant than that of TIG-3 cells with respect to both the number of target sites and the degree of induced changes in transcript expression. The Nucleosome-Seq and ChIP-Seq analyses of histone modifications revealed that the chromatin formed an open structure in regions surrounding the HIF-1a binding sites, but this event occurred prior to the actual binding of HIF1a. Different cellular histories may be encoded by chromatin structures and determine the activation of specific genes in response to hypoxic shock.

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“…Of these classes, lncRNAs with enhancer-like functions were identified using the GENCODE annotation of human genes [30,32]; transcripts mapped to the exons and introns of annotated protein-coding genes, natural antisense transcripts that overlap the protein-coding genes and all known transcripts were excluded. Rinn's lincRNA and HOX cluster lncRNAs were identified according to Rinn's reports [33][34][35].…”

Section: Lncrna Classification and Subgroup Analysismentioning

confidence: 99%

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

Huang

Hao

Bao

et al. 2015

J Assist Reprod Genet

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Purpose To describe the long noncoding RNA (lncRNA) profiles in cumulus cells isolated from polycystic ovary syndrome (PCOS) patients by employing a microarray and in-depth bioinformatics analysis. This information will help us understand the occurrence and development of PCOS. Methods In this study, we used a microarray to describe lncRNA profiles in cumulus cells isolated from ten patients (five PCOS and five normal women). Several differentially expressed lncRNAs were chosen to validate the microarray results by quantitative RT-PCR (qRT-PCR). Then, the differentially expressed lncRNAs were classified into three subgroups (HOX loci lncRNA, enhancer-like lncRNA, and lincRNA) to deduce their potential features. Furthermore, a lncRNA/mRNA co-expression network was constructed by using the Cytoscape software (V2.8.3, http://www.cytoscape.org/). Results We observed that 623 lncRNAs and 260 messenger RNAs (mRNAs) were significantly up-or down-regulated (≥2-fold change), and these differences could be used to discriminate cumulus cells of PCOS from those of normal pat i e n t s . F i v e d i f f e r e n t i a l l y e x p r e s s e d l n c R N A s (XLOC_011402, ENST00000454271, ENST00000433673, ENST00000450294, and ENST00000432431) were selected to validate the microarray results using quantitative RT-PCR (qRT-PCR). The qRT-PCR results were consistent with the microarray data. Further analysis indicated that many differentially expressed lncRNAs were transcribed from chromosome 2 and may act as enhancers to regulate their neighboring protein-coding genes. Forty-three lncRNAs and 29 mRNAs were used to construct the coding-non-coding gene coexpression network. Most pairs positively correlated, and one mRNA correlated with one or more lncRNAs. Conclusions Our study is the first to determine genome-wide lncRNA expression patterns in cumulus cells isolated from PCOS patients by microarray. The results show that clusters of lncRNAs were aberrantly expressed in cumulus cells of PCOS patients compared with those of normal women, which revealed that lncRNAs differentially expressed in PCOS and normal women may contribute to the occurrence of PCOS and affect oocyte development.

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

Cited by 3,701 publications

References 30 publications

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

Genome-wide identification and annotation of HIF-1α binding sites in two cell lines using massively parallel sequencing

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

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