Global Identification of HIF-1α Target Genes in Benzene Poisoning Mouse Bone Marrow Cells
| Autor: | Yunqiu Pu, Rongli Sun, Zhaodi Man, Juan Zhang, Fengxia Sun, Kai Xu, Lihong Yin, Xing Meng, Yuepu Pu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis lcsh:Medicine HIF-1α Bone Marrow Cells Article 03 medical and health sciences Mice benzene ChIP-Seq medicine Animals Humans Binding site Gene Chemistry Hemolytic Agents Cell Cycle lcsh:R Public Health Environmental and Occupational Health hematopoietic toxicity Cell Differentiation Cell cycle Hematopoietic Stem Cells Hypoxia-Inducible Factor 1 alpha Subunit Cell biology Haematopoiesis 030104 developmental biology medicine.anatomical_structure Pyrimidine metabolism Models Animal Bone marrow Stem cell Signal transduction Signal Transduction |
| Zdroj: | International Journal of Environmental Research and Public Health Volume 15 Issue 11 International Journal of Environmental Research and Public Health, Vol 15, Iss 11, p 2531 (2018) |
| ISSN: | 1660-4601 |
| DOI: | 10.3390/ijerph15112531 |
| Popis: | Benzene is a hematopoietic toxicant, and hematopoietic cells in bone marrow (BM) are one of the main targets for its action, especially hematopoietic stem cells (HSCs). Hypoxia-inducible factor-1&alpha (HIF-1&alpha ) is associated with the metabolism and physiological functions of HSCs. We previously found that the mechanism of regulation of HIF-1&alpha is involved in benzene-induced hematopoietic toxicity. In this study, chromatin immunoprecipitation sequencing (ChIP-Seq) technologies were used to analyze the genome-wide binding spectrum of HIF-1&alpha in mouse BM cells, and specific HIF-1&alpha target genes and pathways associated with benzene toxicity were screened and validated. By application of the ChIP-Seq technique, we identified target genes HIF-1&alpha directly binds to and regulates. Forty-two differentially down-regulated genes containing the HIF-1&alpha specific binding site hypoxia response element (HRE) were found, of which 25 genes were with biological function. Moreover, the enrichment analysis of signal pathways indicated that these genes were significantly enriched in the Jak-STAT signaling pathway, Natural killer cell mediated cytotoxicity, the Fc epsilon RI signaling pathway, Pyrimidine metabolism, the T cell receptor signaling pathway, and Transcriptional misregulation in cancer. After verification, 11 genes involved in HSC self-renewal, cell cycle, differentiation, and apoptosis pathways were found to be significantly reduced, and may participate in benzene-induced hematotoxicity. Our study provides a new academic clue for the mechanism of benzene hematotoxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|