Interplay between Chromatin Remodeling and Epigenetic Changes during Lineage-Specific Commitment to Granzyme B Expression

Interplay between Chromatin Remodeling and Epigenetic Changes during Lineage-Specific Commitment to Granzyme B Expression
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DOI:
10.4049/jimmunol.0901522
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发表时间:
2009-12-01
影响因子:
4.4
通讯作者:
Rao, Sudha
Rao, Sudha
中科院分区:
医学2区
文献类型:
--
作者:
Juelich, Torsten;Sutcliffe, Elissa;Rao, Sudha

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染色质重塑和组蛋白翻译后修饰的作用是相互联系的.在获得细胞特异性功能的过程中控制基因表达的机制知之甚少。我们发现,在体外活化CD 4(+)和CD 8(+)T淋巴细胞后,两种细胞类型均显示颗粒酶B(gzm B)近端启动子区域的组蛋白H3快速丢失。然而,尽管gzmB近端启动子在两个T细胞亚群中被重塑,但只有CD 8(+)T细胞表达高水平的gzmB,并显示出关键表观遗传标记的独特模式,特别是差异H3乙酰化和甲基化。这些数据表明,为了使高水平的转录发生,除了在gzmB的近端启动子处的组蛋白损失之外,还需要建立一组不同的组蛋白修饰。免疫学杂志,2009,183:7063-7072.
The role of chromatin remodeling and histone posttranslational modifications and bow they are integrated. to control gene expression during the acquisition of cell-specific functions is poorly understood. We show here that following in vitro activation of CD4(+) and CD8(+) T lymphocytes, both cell types show rapid histone H3 loss at the granzyme B (gzmB) proximal promoter region. However, despite the gzmB proximal promoter being remodeled in both T cell subsets, only CD8(+) T cells express high levels of gzmB and display a distinct pattern of key epigenetic marks, notably differential H3 acetylation and methylation. These data suggest that for high levels of transcription to occur a distinct set of histone modifications needs to be established in addition to histone loss at the proximal promoter of gzmB. The Journal of Immunology, 2009, 183: 7063-7072.