Abstract
Long noncoding RNAs (lncRNAs) are a new class of noncoding RNAs that have been extensively studied in the recent past as a regulator of gene expression, including modulation of epigenetic regulation. The lncRNAs class encompasses a number of subclasses, classified based on their genomic loci and relation to protein-coding genes. Functional differences between subclasses have been increasingly studied in the recent years, though the regulation of expression and biogenesis of lncRNAs have been poorly studied. The availability of genome-scale datasets of epigenetic marks has motivated us to understand the patterns and processes of epigenetic regulation of lncRNAs. Here we analysed the occurrence of expressive and repressive histone marks at the transcription start site (TSS) of lncRNAs and their subclasses, and compared these profiles with that of the protein-coding regions. We observe distinct differences in the density of histone marks across the TSS of a few lncRNA subclasses. The sense-intronic lncRNA subclass showed a paucity for mapped histone marks across the TSS which were significantly different than all the lncRNAs and protein-coding genes in most cases. Similar pattern was also observed for the density of transcription factor binding sites (TFBS). These observations were generally consistent across cell and tissue types. The differences in density across the promoter were significantly associated with the expression level of the genes, but the differences between the densities across long noncoding and protein-coding gene promoters were consistent irrespective of the expression levels. Apart from suggesting general differences in epigenetic regulatory marks across long noncoding RNA promoters, our analysis suggests a possible alternative mechanism of regulation and/or biogenesis of sense-intronic lncRNAs.
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Acknowledgements
The authors acknowledge the discussions with Dr. Sheetal Gandotra which considerably improved thought process and content of the manuscript. SSa and SG acknowledges a Senior Research Fellowship from the Council of Scientific and Industrial Research, India. This work was funded by the Council of Scientific and Industrial Research, India through project GENCODE-C (BSC0123). We acknowledge the NIH Roadmap to Epigenomics Consortium members for producing the data used in our analysis procedures. We are thankful to NIH Roadmap, Epigenomics Consortium for maintaining an open access to the datasets deposited in NIH Roadmap Epigenomics Project Data Listings at http://nihroadmap.nih.gov/epigenomics/.
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[Ghosh S., Sati S., Sengupta S. and Scaria V. 2015 Distinct patterns of epigenetic marks and transcription factor binding sites across promoters of sense-intronic long noncoding RNAs. J. Genet. 94, xx–xx]
Sourav Ghosh and Satish Sati contributed equally to this work.
VS and SSe designed the analysis pipeline and coordinated the study. VS and SSe wrote the manuscript. Bioinformatics analysis was carried out by VS, SG and SSe.
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GHOSH, S., SATI, S., SENGUPTA, S. et al. Distinct patterns of epigenetic marks and transcription factor binding sites across promoters of sense-intronic long noncoding RNAs. J Genet 94, 17–25 (2015). https://doi.org/10.1007/s12041-015-0484-2
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DOI: https://doi.org/10.1007/s12041-015-0484-2