Histone H3 amino-terminal tail phosphorylation and acetylation: Synergistic or independent transcriptional regulatory marks?
Histone H3 amino-terminal tail phosphorylation and acetylation: Synergistic or independent transcriptional regulatory marks?
复制标题
DOI：
10.1101/sqb.2004.69.219
复制
发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Peterson, CL
中科院分区：
文献类型：
--
作者：
Fry, CJ;Shogren-Knaak, MA;Peterson, CL
* 这些作者对这项工作作出了同样的贡献。canoylphorbol 13-acetate（TPA）（Mahadevan et al. 1991）。令人惊讶的是，作者将组蛋白H3确定为MAP激酶级联的关键下游靶点，这表明组蛋白H3磷酸化有助于立即早期基因的激活。组蛋白H3的磷酸化对转录抑制剂α-鹅膏蕈碱具有抗性，这表明H3的磷酸化不是转录的结果，而是在有丝分裂原刺激后传递到染色质的调节信号。这一点后来被研究证实，研究表明，用激酶抑制剂预处理细胞或删除组蛋白H3激酶可减少有丝分裂原刺激后c-fos和cjun的活化（Soloaga et al. 2003）。这些研究提供了第一个证据，将组蛋白H3磷酸化与转录激活联系起来。除了组蛋白H1之外，组蛋白H3早已被认为在有丝分裂期间当染色体浓缩时被全面磷酸化（对于最近的综述，参见Prigent和Dimitrov 2003）。与有丝分裂不同，立即早期基因激活期间的组蛋白H3磷酸化仅发生在一小部分核小体上，并且针对活性基因。使用从Coffin-Lowry综合征（CLS）患者中建立的成纤维细胞进行的研究表明，Rsk-2是参与细胞生长控制的pp 90 rsk激酶家族的成员，是在即刻早期基因激活期间负责磷酸化组蛋白H3的下游效应激酶（Sassone-Corsi et al. 1999）。然而，最近的研究强烈暗示有丝分裂原刺激激酶Msk 1和Msk 2（Wiggin et al. 2002; Soloaga et al. 2003）。组蛋白H3磷酸化，一个与浓缩染色体相关的标记，如何促进转录激活？答案是在很久以后，随着组蛋白修饰特异性抗体和染色质免疫沉淀技术的出现。
* These authors contributed equally to this work. canoylphorbol 13-acetate (TPA)(Mahadevan et al. 1991). Surprisingly, the authors identified histone H3 as a key downstream target of the MAP kinase cascade, suggesting that histone H3 phosphorylation contributes to the activation of immediate-early genes. Phosphorylation of histone H3 was resistant to the transcriptional inhibitor α-amanitin, suggesting that phosphorylation of H3 was not a consequence of transcription, but rather a regulatory signal delivered to chromatin upon stimulation with mitogens. This was later confirmed by studies showing that pretreatment of cells with kinase inhibitors or deletion of the histone H3 kinase reduced activation of c-fos and cjun upon mitogen stimulation (Soloaga et al. 2003). These studies provided the first evidence linking histone H3 phosphorylation to transcriptional activation. Histone H3, in addition to histone H1, had long been known to be globally phosphorylated during mitosis when chromosomes are condensed (for a recent review, see Prigent and Dimitrov 2003). Unlike mitosis, histone H3 phosphorylation during immediate-early gene activation occurs on only a small fraction of nucleosomes and is targeted to active genes. Studies using fibroblasts established from Coffin–Lowry Syndrome (CLS) patients suggested that Rsk-2, a member of the pp90rsk family of kinases implicated in cell growth control, was the downstream effector kinase responsible for phosphorylating histone H3 during activation of immediate-early genes (Sassone-Corsi et al. 1999). However, more recent studies strongly implicate the mitogen-stimulated kinases Msk1 and Msk2 (Wiggin et al. 2002; Soloaga et al. 2003). How does histone H3 phosphorylation, a mark associated with condensed chromosomes, facilitate transcriptional activation? The answers came much later with the advent of histone modification-specific antibodies and chromatin immunoprecipitation techniques.