Global Identification of HIF-1α Target Genes in Benzene Poisoning Mouse Bone Marrow Cells.

摘要: Benzene is a hematopoietic toxicant, and cells in bone marrow (BM) are one of the main targets for its action, especially stem (HSCs). Hypoxia-inducible factor-1α (HIF-1α) associated with metabolism physiological functions HSCs. We previously found that mechanism regulation HIF-1α involved benzene-induced toxicity. In this study, chromatin immunoprecipitation sequencing (ChIP-Seq) technologies were used to analyze genome-wide binding spectrum mouse BM cells, specific target genes pathways benzene toxicity screened validated. By application ChIP-Seq technique, we identified directly binds regulates. Forty-two differentially down-regulated containing site hypoxia response element (HRE) found, which 25 biological function. Moreover, enrichment analysis signal indicated these significantly enriched Jak-STAT signaling pathway, Natural killer cell mediated cytotoxicity, Fc epsilon RI Pyrimidine metabolism, T receptor Transcriptional misregulation cancer. After verification, 11 HSC self-renewal, cycle, differentiation, apoptosis be reduced, may participate hematotoxicity. Our study provides new academic clue