Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital Boston, and Harvard Medical School, Binney Street, Boston, MA 02115, USA.
Genome Biol. 2009;10(10):R113. doi: 10.1186/gb-2009-10-10-r113. Epub 2009 Oct 14.
Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes transactivated by hypoxia in two cell lines.
We found that when cells were acutely subjected to hypoxia, HIF-1 preferentially bound to loci that were already transcriptionally active under normal growth conditions characterized by the presence of histone H3 lysine 4 methylation, the presence of RNA polymerase II, and basal production of mRNA. Cell type-specific differences in HIF-1 binding were largely attributable to differences in the basal gene expression patterns in the cells prior to the onset of hypoxia.
These results suggest that the repertoire of genes active in a cell (for example, through lineage specific transcription factors) defines the subset of genes that are permissive for binding and transactivation by stimulus-responsive transcription factors.
缺氧诱导因子 1（HIF-1）在细胞对缺氧的适应中起着关键作用。为了更好地理解 HIF-1 结合和转录激活的决定因素，我们使用 ChIP-chip 和基因表达谱分析来定义两个细胞系中缺氧时 HIF-1 结合和受转录激活的基因与表观遗传景观、HIF-1 结合位点之间的关系。
我们发现，当细胞急性缺氧时，HIF-1 优先结合在正常生长条件下已经转录活跃的基因座上，这些基因座的特征是组蛋白 H3 赖氨酸 4 甲基化、RNA 聚合酶 II 的存在和基础 mRNA 的产生。HIF-1 结合的细胞类型特异性差异主要归因于细胞在缺氧发生前的基础基因表达模式的差异。
这些结果表明，细胞中活跃的基因（例如，通过谱系特异性转录因子）定义了受刺激反应性转录因子结合和转录激活允许的基因子集。
