H19 is a maternally-expressed imprinted gene that encodes long non-coding RNA. Chromatin immunoprecipitation (ChIP)-sequencing analyses of human adipose-derived stem cells (hADSCs) showed that hypoxia induced trimethylation of 4^th lysine residue of histone 3 (H3K4me3) in the H19 gene, among the 40 known human imprinted genes, to the greatest extent. We investigated whether hypoxia changed the DNA and histone methylation levels of the imprinted H19 gene in an allele-specific (AS) manner. Using AS primer sets for the human H19 gene, we conducted ChIP-quantitative polymerase chain reaction, which revealed that hypoxia increased the active histone marks, H3K4me3 and H3K9/14Ac, in one allele (named B allele) but not in the other allele (named A allele). In contrast, hypoxia did not change the H3K9me3 levels in either allele. Hypoxia-inducible factor 1 (HIF-1) directly bound to the H19 promoter only in the B allele. HIF-1α knock-down prevented the increase in the active histone modification and mRNA expression of the B allele under hypoxia, indicating that HIF-1α caused AS changes in the histone modification of the H19 gene. Long-term hypoxia did not change the AS DNA methylation throughout the cell cycle. Thus, hypoxia changed the histone modification of the active allele in an HIF-1α-dependent manner, without changing the imprinted status of the H19 gene.

H19是母体表达的印迹基因，可编码长的非编码RNA。人类脂肪干细胞（hADSCs）的染色质免疫沉淀（ChIP）测序分析表明，低氧诱导了40种已知的人类印迹基因中H19基因中组蛋白3（H3K4me3）的^第4^个赖氨酸残基的三甲基化。程度。我们调查了缺氧是否以等位基因特异性（AS）的方式改变了印迹H19基因的DNA和组蛋白甲基化水平。对人类H19使用AS引物对基因，我们进行了ChIP定量聚合酶链反应，揭示了低氧增加了一个等位基因（命名为B等位基因）中的活性组蛋白标记H3K4me3和H3K9 / 14Ac，而在另一个等位基因（命名为A等位基因）中则没有。相反，缺氧并没有改变两个等位基因中的H3K9me3水平。缺氧诱导因子1（HIF-1）仅在B等位基因中直接与H19启动子结合。HIF-1α敲低阻止了缺氧条件下B等位基因的活性组蛋白修饰和mRNA表达的增加，表明HIF-1α导致H19组蛋白修饰的AS变化基因。长期缺氧不会改变整个细胞周期的AS DNA甲基化。因此，缺氧以HIF-1α依赖性方式改变了活性等位基因的组蛋白修饰，而没有改变H19基因的印迹状态。