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Use for regulating specific transcriptional activity by HDAC2 during TPA-induced HL-60 cell differentiation

机译:用于在TPA诱导的HL-60细胞分化过程中通过HDAC2调节特异性转录活性

摘要

The present invention relates to the use of 12-O-tetradecanoylphorbol-13-acetate (TPA) -induced leukemia cell differentiation during HDC2 specific transcriptional activity regulation. The human myeloid leukemia cell line HL-60 differentiates into monocytes when treated with TPA. However, the mechanism of differentiation of the cells relative to TPA has not been clarified. We performed ChIP-seq profiling of RNA Pol II, HDAC2, Acetyl H3 (AcH3) and H3K27me3, and analyzed differential chromatin state changes during TPA-induced differentiation of HL-60 cells. We focused on anomalous activated genes that appear to have improved H3 acetylation despite increased HDAC2 collection. We found that in a histone deacetylase activity-independent manner, HDAC2 positively regulates the expression of these genes. In conclusion, the present invention revealed a specific-chromatin state during HL-60 cell differentiation after TPA exposure. As a diacetylase activity-independent pathway, HDAC2 can activate transcription of specific genes through interaction with PAX5. Found out.
机译:本发明涉及在HDC2特异性转录活性调节过程中12-O-十四烷酰佛波醇-13-乙酸酯(TPA)诱导的白血病细胞分化的用途。用TPA处理时,人骨髓白血病细胞系HL-60分化为单核细胞。然而,尚未阐明细胞相对于TPA的分化机制。我们进行了RNA Pol II,HDAC2,乙酰基H3(AcH3)和H3K27me3的ChIP-seq分析,并分析了TPA诱导的HL-60细胞分化过程中染色质状态的差异。我们集中研究了异常激活的基因,这些基因尽管增加了HDAC2的收集,但似乎改善了H3的乙酰化作用。我们发现,以组蛋白脱乙酰基酶活性独立的方式,HDAC2积极调节这些基因的表达。总之,本发明揭示了TPA暴露后HL-60细胞分化过程中的特定染色质状态。作为不依赖于二乙酰酶活性的途径,HDAC2可以通过与PAX5相互作用激活特定基因的转录。发现。

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