Functionality of Intergenic Transcription: An Evolutionary Comparison

Khaitovich, Philipp; Kelso, Janet; Franz, Henriette; Visagie, Johann; Giger, Thomas; Joerchel, Sabrina; Petzold, Ekkehard; Green, Edward; Lachmann, Michael; Pääbo, Svante

doi:10.1371/journal.pgen.0020171

Cited by 78 publications

(71 citation statements)

References 23 publications

(46 reference statements)

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“…These findings are consistent with an earlier study that showed conserved tissue-specific intergenic transcription between human and chimpanzee in brain, heart, and testis (Khaitovich et al 2006). Conservation of tissue specificity of lincRNAs might be an indirect effect through coregulation with mRNAs.…”

Section: Conservation Of Lincrna Tissue Specificitysupporting

confidence: 93%

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals

2014

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Long intergenic noncoding RNAs (lincRNAs) play diverse regulatory roles in human development and disease, but little is known about their evolutionary history and constraint. Here, we characterize human lincRNA expression patterns in nine tissues across six mammalian species and multiple individuals. Of the 1898 human lincRNAs expressed in these tissues, we find orthologous transcripts for 80% in chimpanzee, 63% in rhesus, 39% in cow, 38% in mouse, and 35% in rat. Mammalian-expressed lincRNAs show remarkably strong conservation of tissue specificity, suggesting that it is selectively maintained. In contrast, abundant splice-site turnover suggests that exact splice sites are not critical. Relative to evolutionarily young lincRNAs, mammalian-expressed lincRNAs show higher primary sequence conservation in their promoters and exons, increased proximity to protein-coding genes enriched for tissue-specific functions, fewer repeat elements, and more frequent single-exon transcripts. Remarkably, we find that~20% of human lincRNAs are not expressed beyond chimpanzee and are undetectable even in rhesus. These hominid-specific lincRNAs are more tissue specific, enriched for testis, and faster evolving within the human lineage.

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Section: Conservation Of Lincrna Tissue Specificitysupporting

confidence: 93%

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals

2014

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“…[28][29][30] Similarly, by whole chromosome RNA analysis it has been observed that about 93% of the human genome sequence is pervasively transcribed in one or the other cell type. [31][32][33][34][35] Maximum of these transcripts are logically expected to be the "dark matter" of the genome or ncRNAs of diverse biological functions. 36 Recently, a class of small regulatory RNAs called piRNAs (PIWI-interacting RNAs) have been reported to function for silencing of transposons in the germline.…”

Section: Long Interspersed Nuclear Elements (Lines)mentioning

confidence: 99%

Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

Singh

Rath²

2012

RNA Biology

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“…Nevertheless, their expression patterns may be conserved among tissues or along developmental axes. 14,15 More importantly, ncRNA function in gene regulation has emerged as an important mechanism in the control of many biologic processes in development and carcinogenesis. 16 In the present study, we have identified intergenic transcription of a unique long ncRNA, here termed HOTAIRM1 (HOTAIR myeloid 1) after the nomenclature of Rinn et al, 7 located between the human HOXA1 and HOXA2 genes.…”

Section: Introductionmentioning

confidence: 99%

A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster

Zhang

Zheng²,

Padden

et al. 2009

Blood

327

344

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We have identified an intergenic transcriptional activity that is located between the human HOXA1 and HOXA2 genes, shows myeloid-specific expression, and is upregulated during granulocytic differentiation. The novel gene, termed HOTAIRM1 (HOX antisense intergenic RNA myeloid 1), is transcribed antisense to the HOXA genes and originates from the same CpG island that embeds the start site of IntroductionHuman HOX gene clusters are known for the prevalence of intergenic transcription between coding genic members. 1 Similar activity has also been observed in other developmentally important or tissue-specific gene loci, such as those containing the human beta globin genes, cardiac myosin heavy chain genes, and the interleukin-4 (IL-4)/IL-13 gene cluster. [2][3][4] Extensive HOX gene cluster intergenic transcripts have been described largely as noncoding RNAs (ncRNAs), including both short microRNA (miRNA) species and long ncRNAs that are antisense to their canonical HOX neighbors. Well-defined HOX region ncRNAs include the mir-10 and mir-196 paralogs, bithoraxoid ncRNAs of the Drosophila bithorax complex, and human HOX antisense intergenic RNA (HOTAIR). [5][6][7] Intergenic regions have been proposed as locations for novel radiational and reorganizing changes that have occurred in the evolution of HOX gene clusters, which are relatively constrained in structure in the higher vertebrates. 5,8 Several recent studies have focused on expression of intergenic ncRNAs in the human HOX regions, especially the HOXA cluster, in tumor cell lines, tissues, and fibroblasts from different anatomic origins. All reported unusually active transcription within the intergenic regions, occurring in patterns coordinated with their HOX neighbors. 7,9,10 Intergenic ncRNAs in the HOXA gene cluster were usually associated with CpG islands and their expression accompanied changes in either polycomb group repressive complex binding or methylation of histones, suggesting a pattern of cis modulation of the intergenic transcripts before the activation of adjacent HOX genes. However, the HOTAIR transcript, located between HOXC11 and HOXC12, was found to function in trans to repress a distal group of homologous HOXD genes by demarcating an extended silenced domain through interaction with the polycomb group complex PRC2 histone methyltransferase 7,10,11 De novo genomic transcription mapping has revealed that intergenic ncRNA is possibly the most abundant form of transcriptional output from the genomes of humans and other higher eukaryotic organisms. 12,13 Within the human genome, the majority of intergenic ncRNA are not highly conserved at the sequence level, with long ncRNAs generally less conserved than short miRNAs. Nevertheless, their expression patterns may be conserved among tissues or along developmental axes. 14,15 More importantly, ncRNA function in gene regulation has emerged as an important mechanism in the control of many biologic processes in development and carcinogenesis. 16 In the present study, we have identified intergenic transc...

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Functionality of Intergenic Transcription: An Evolutionary Comparison

Cited by 78 publications

References 23 publications

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals

Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster

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