Transcription factor HIF1A downstream targets associated pathways polymorphic hypoxia response element (HRE) sites and initiative for standardization

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November 2016,Volume 37,Issue 11,pp 1485114861Cite as

Transcription factor HIF1A: downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature

Hypoxia-inducible factor-1 (HIF-1) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1 target genes (HIF-1-TGs) is important for understanding the adapting mechanism. The aim of the present study was to collect known HIF-1-TGs and identify their associated pathways. Targets and associated genomics data were retrieved using PubMed, WoS (), HGNC (), NCBI (), Ensemblv.84 (), DAVID Bioinformatics Resources (/), and Disease Ontology database (). From 51 papers, we collected 98 HIF-1 TGs found to be associated with 20 pathways, includingmetabolism of carbohydratesandpathways in cancer. Reanalysis of genomic coordinates of published HREs (hypoxia response elements) revealed six polymorphisms within HRE sites (HRE-SNPs):ABCG2,ACE,CA9, andCP. Due to large heterogeneity of results presentation in scientific literature, we also propose a first step towards reporting standardization of HIF-1-target interactions consisting of ten relevant data types. Suggested minimal checklist for reporting will enable faster development of a complete catalog of HIF-1-TGs, data sharing, bioinformatics analyses, and setting novel more targeted hypotheses. The proposed format for data standardization is not yet complete but presents a baseline for further optimization of the protocol with additional details, for example, regarding the experimental validation.

The online version of this article (doi:10.1007/s1-4) contains supplementary material, which is available to authorized users.

This work was supported by the Slovenian Research Agency (ARRS) through the Research program (P4-0220).

. Identified polymorphisms within HRE sites of four target genes. Sequence of the target genes:

(D). Biotype of identified polymorphisms within HRE sites (E). (DOCX 1512 kb)

. Collected data associated with 98 HIF-1 target genes. (XLSX 38 kb)

. Pathway analysis of HIF-1 downstream targets. (DOCX 17 kb)

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Biotechnical Faculty, Department of Animal Science

Slemc, L. & Kunej, T. Tumor Biol. (2016) 37: 14851.

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