title: Decrypting ENCODEd epigenetic marks of human tRN-A-RS genes in normal, stem and cancer cell lines.
abstract: Screening large-scale ENCODE data of 625 cytoplasmic transfer RNA (tRNAs) and 37 aminoacyl tRNA synthetase (AARSs) human genes, we deconstruct the array of relations between 10 histone marks affecting 15 chromatin states; their tissue specificity and variations and interchange amongst normal, cancerous and stem cells. The histone marks of RNA Pol II transcribed AARS genes share, but also contrast with that on RNA Pol III transcribed tRNA genes. tRNAs with identical/similar sequences may be in significantly varying states even within the same cell line; the chromatin scaffold, where the tRNA gene resides, is the key determinant. Hepatocellular carcinoma cell line has dominant H3K27me3, and singular clustering of other marks. Leukaemic cell line has hyperactive genes. The quiescence of the stem cells is encoded in the markers. Leaving aside the important exceptions in stem cells and elsewhere, tRNAs with cove scores above 50 have active markers and precise sets of transcription factors, and are usually well conserved compared to the low-scoring ones. Pseudo tRNAs are in heterochromatin/repressed state with anomalous exceptions in cancer cells. We motivate that Epigenetic-Phishing hacks the translation apparatus through the chromatin states governed by the histone marks of tRNA and AARS genes, and speculate on their therapeutic implications in cancer and on stem cells.
authors.affiliation: a Computational Biology Group , Indian Association for the Cultivation of Science , Jadavpur , Kolkata 700032 , India.
authors.forename: Sanga
authors.initials: S
authors.lastname: Mitra
authors.affiliation: b Computational & Systems Biology, Cancer Genomics, & Molecular Biophysics , University of Massachusetts , Boston , MA 02125 , USA.
authors.forename: Arpa
authors.initials: A
authors.lastname: Samadder
authors.affiliation: c Structural Biology & Bioinformatics Division , Indian Institute of Chemical Biology , Kolkata 700032 , India.
authors.forename: Pijush
authors.initials: P
authors.lastname: Das
authors.affiliation: d Department of Genetics , University of Georgia , Athens , GA 30602 , USA.
authors.forename: Smarajit
authors.initials: S
authors.lastname: Das
authors.affiliation: e Department of Biochemistry , University of Nebraska-Lincoln , Lincoln , NE 68588 , USA.
authors.forename: Medhanjali
authors.initials: M
authors.lastname: Dasgupta
authors.affiliation: a Computational Biology Group , Indian Association for the Cultivation of Science , Jadavpur , Kolkata 700032 , India.|f Gyanxet , BF 286 Salt Lake, Kolkata 700064 , India.
authors.forename: Jayprokas
authors.initials: J
authors.lastname: Chakrabarti
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D006367:HeLa Cells; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020014:K562 Cells; D008113:Liver Neoplasms / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002843:Chromatin; D014157:Transcription Factors; D012343:RNA, Transfer; D012319:RNA Polymerase II; D000604:Amino Acyl-tRNA Synthetases
keywords: AARS; RNA polymerase II; RNA polymerase III; chromatin state segmentation; histone modifications; tRNA