Dataset Information

EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes.

ABSTRACT: Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which contain the regulation part of the retrovirus. Remaining HERVs constitute 7% to 8% of the present day human genome, and most have been identified as solo LTRs. The HERV sequences have been associated with several molecular functions as well as certain diseases in human, but their roles in human diseases are yet to be established. We designed EnHERV to make accessible the identified endogenous retrovirus repetitive sequences from Repbase Update (a database of eukaryotic repetitive elements) that are present in the human genome. Defragmentation process was done to improve the RepeatMasker annotation output. The defragmented elements were used as core database in EnHERV. EnHERV is available at http://sysbio.chula.ac.th/enherv and can be searched using either gene lists of user interest or HERV characteristics. Besides the search function, EnHERV also provides an enrichment analysis function that allows users to perform enrichment analysis between selected HERV characteristics and user-input gene lists, especially genes with the expression profile of a certain disease. EnHERV will facilitate exploratory studies of specific HERV characteristics that control gene expression patterns related to various disease conditions. Here we analyzed 25 selected HERV groups/names from all four HERV superfamilies, using the sense and anti-sense directions of the HERV and gene expression profiles from 49 specific tissue and disease conditions. We found that intragenic HERVs were associated with down-regulated genes in most cancer conditions and in psoriatic skin tissues and associated with up-regulated genes in immune cells particularly from systemic lupus erythematosus (SLE) patients. EnHERV allowed the analysis of how different types of LTRs were differentially associated with specific gene expression profiles in particular disease conditions for further studies into their mechanisms and functions.

SUBMITTER: Tongyoo P

PROVIDER: S-EPMC5417679 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes.

Tongyoo Pumipat P Avihingsanon Yingyos Y Prom-On Santhitham S Mutirangura Apiwat A Mhuantong Wuttichai W Hirankarn Nattiya N

PloS one 20170504 5

Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which contain the regulation part of the retrovirus. Remaining HERVs constitute 7% to 8% of the present day human genome, and most have been identified as solo LTRs. The HERV sequences have been associated with several molecular functions as well as certain diseases in human, but their roles in human diseases are yet to be established. We designed EnHERV to make accessible the identified endogenous retrovirus repe ...[more]

PMID: 28472109

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Project description:Under physiological conditions, most human endogenous retroviruses (HERVs) are transcriptionally silent. However, re-activation of HERVs is observed under pathological conditions like inflammation or cancer. In addition to expression of HERV sequences, an impact of HERV-loci on expression of adjacent genes has been suggested as probably important patho-physiological mechanism. A candidate for such a gene is PRODH (proline dehydrogenase 1), which is located on chromosome 22 adjacent to HERVK-24. Germ cell tumors (GCTs) are known to express high level of HERVK sequences. In addition, non-seminomatous GCT are useful models to study HERV expression in the context of differentiation since they reflect aspects of cellular development during embryogenesis and usually contain different cell types. This is due to the embryonal carcinoma (EC) cells, which are the stem cell component of GCT. They are pluripotent, show high expression of pluripotency markers like OCT4 and LIN28A and can differentiate into either somatic derivatives (teratoma cells) or choriocarcinoma or yolk-sac tumor cells reflecting extra-embryonal differentiation. OCT4 is lost upon differentiation. We used GCT derived cell lines of varying differentiation stages to analyze expression of HERVK and PRODH. Differentiation status and cellular relationship of GCT cells was determined using microarray analysis and western blotting of the embryonic pluripotency markers OCT4 and LIN28A. The highest expression of HERVK was found in undifferentiated EC cells, which retain a stem cell phenotype and express both OCT4 and LIN28. In contrast, the lowest expression of HERVK was observed in somatic differentiated GCT cells which also lack OCT4 and LIN28A whereas GCT cells with differentiation characteristics of yolk-sac tumor expressed LIN28A but not OCT4 and showed intermediate level of HERVK. A similar pattern was found for PRODH. Differentiation of EC cells by siRNA mediated knock-down of OCT4 or treatment with differentiation inducing medium decreased expression of HERVK and PRODH. Treatment of differentiated GCT cells with 5'-azacytidine and trichostatin A increased expression of HERVK and PRODH, indicating that epigenetic mechanisms are responsible for altered expression of these genes. Our data suggest that HERVK expression is dependent on cellular differentiation stages regulated by epigenetic mechanisms, which can also affect expression of neighboring genes.

Dataset Information

EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes.

Publications

EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes.

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