P-STAT1 mediates higher-order chromatin remodelling of the human MHC in response to IFNγ
P-STAT1 mediates higher-order chromatin remodelling of the human MHC in response to IFNγ
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DOI：
10.1242/jcs.012328
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发表时间：
2007-09-15
影响因子：
4
通讯作者：
Sheer, Denise
中科院分区：
文献类型：
--
作者：
Christova, Rossitza;Jones, Tania;Sheer, Denise
IFN γ对主要组织相容性复合体（MHC）的转录激活是细胞介导免疫的关键步骤。在IFN γ诱导的早期阶段，携带整个MHC位点的染色质从6号染色体区域环出。我们在这里表明，JAK/STAT信号触发这种高阶染色质重塑，整个MHC位点在经典HLA II类基因的转录激活之前变得去密集。阻止磷酸化的STAT1单点突变足以消除染色质重塑，从而在JAK/STAT信号通路和人类染色质结构之间建立直接联系。染色质重构的开始与活化的STAT1和染色质重构酶BRG1在MHC内特定位点的结合相对应，随后是rna聚合酶募集和组蛋白超乙酰化。我们提出MHC位点的高阶染色质重塑是为经典HLA基因的后续激活产生转录许可染色质环境的必要步骤。
Transcriptional activation of the major histocompatibility complex (MHC) by IFN gamma is a key step in cell-mediated immunity. At an early stage of IFN gamma induction, chromatin carrying the entire MHC locus loops out from the chromosome 6 territory. We show here that JAK/STAT signalling triggers this higher-order chromatin remodelling and the entire MHC locus becomes decondensed prior to transcriptional activation of the classical HLA class II genes. A single point mutation of STAT1 that prevents phosphorylation is sufficient to abolish chromatin remodelling, thus establishing a direct link between the JAK/STAT signalling pathway and human chromatin architecture. The onset of chromatin remodelling corresponds with the binding of activated STAT1 and the chromatin remodelling enzyme BRG1 at specific sites within the MHC, and is followed by RNA-polymerase recruitment and histone hyperacetylation. We propose that the higher-order chromatin remodelling of the MHC locus is an essential step to generate a transcriptionally permissive chromatin environment for subsequent activation of classical HLA genes.