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Epigenetics and Gene Expression ‐ Pathways, Pathway Suites and Networks at RGD's Pathway Portal
Author(s) -
Petri Victoria,
Hayman G. Thomas,
Smith Jennifer R,
Tutaj Marek,
Thota Jyothi,
De Pons Jeff,
Dwinell Melinda R,
Shimoyama Mary
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.593.2
Subject(s) - epigenetics , chromatin , biology , microrna , histone , computational biology , chromatin remodeling , biological pathway , dna methylation , regulation of gene expression , genetics , gene , gene expression , microbiology and biotechnology
Epigenetic changes, the modification of DNA and histones and the remodeling of chromatin, are instrumental for the differential expression of genes. They also impact on DNA damage response and repair systems, and are affected by aging and in disease. RGD's Pathway Portal offers an expanding collection of interactive diagram pages along with accompanying annotations for metabolic, signaling, regulatory and drug pathways, disease pathways and associated altered pathways. Pathways directly connected are displayed on the page and can be accessed via the Pathway Ontology. Those that globally revolve around abroader concept are brought together within a pathway suite; a pathway suite network combines two or more pathway suites. The pathways of histone and DNA modification are presented in individual diagrams; the four chromatin remodeling pathways are individually described in the synopsis, and collectively displayed in the diagram page. The epigenetic pathways represent one suite component of the Gene Expression and Regulation Pathway Suite Network. The other two suites in the network are devoted to transcription by the three polymerases and the transcription‐coupled splicing, and to RNA‐ and translation‐related pathways, respectively. Differential DNA methylation and chromatin modification, and differential expression of microRNA (miRNAs) are observed in normal ageing. These changes may be different in the disease state and have been reported for cancer and neurodegenerative diseases. Such changes are described in the ‘Epigenetics, miRNAs’ section of the synopsis for Parkinson disease (PD) pathway page. Several pathways and culprit genes affecting them are shown on the page; they link to pathway ontology report or gene report pages, respectively. As an example, alpha‐synuclein (SNCA), a major contributorto PD, interacts with Dnmt1 DNA methylase whose sequestration from the nucleus leads to global hypomethylation; the inhibitory SNCA effect on DNA modification pathway is shown. An icon for miRNA of potential interest to PD accesses a list with down‐regulated and up‐regulated miRNAs, in turn providing link(s) to the gene report page(s) for the human miRNA. The chromatin modification and microRNA pathways are also present in the Parkinson Disease Pathway Suite. Other pathways in this suite represent components of mitochondrial and calcium homeostasis, and the biosynthesis of and signaling by dopamine. RGD's Pathway Portal is a rich, continually expanding, resource of pathway data. The pathway ontology and the pathway annotation files for the human, rat and mouse genes are available for download from the ftp site. Subsets of annotations can also be downloaded from the ontology report and the pathway diagram pages. The diagram pages along with suites and networks offer an in‐depth view of pathways within a systems biology context. Support or Funding Information RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.Parkinson disease pathway