Koop Ronald, Di Croce Luciano, Beato Miguel
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität, E.-Mannkopff-Strasse 2, D-35033 Marburg, Germany.
EMBO J. 2003 Feb 3;22(3):588-99. doi: 10.1093/emboj/cdg052.
Minichromosomes assembled on the mouse mammary tumor virus (MMTV) promoter in vitro exhibit positioned nucleosomes, one of which covers the binding sites for progesterone receptor (PR) and nuclear factor 1 (NF1). Incorporation of histone H1 into MMTV minichromosomes improves the stability of this nucleosome and decreases basal transcription from the MMTV promoter, as well as its response to either PR or NF1. However, histone H1-containing minichromosomes display better PR binding and support a more efficient synergism between PR and NF1, leading to enhanced transcription initiation. A mutant MMTV promoter lacking positioned nucleosomes does not display enhanced transcriptional synergism in the presence of H1. Binding of PR leads to phosphorylation of H1, which leaves the promoter upon transcription initiation. Thus, H1 assumes a complex and dynamic role in the regulation of the MMTV promoter.
在体外组装于小鼠乳腺肿瘤病毒(MMTV)启动子上的微型染色体呈现出定位核小体,其中一个核小体覆盖了孕激素受体(PR)和核因子1(NF1)的结合位点。将组蛋白H1掺入MMTV微型染色体可提高该核小体的稳定性,并降低MMTV启动子的基础转录及其对PR或NF1的反应。然而,含有组蛋白H1的微型染色体显示出更好的PR结合,并支持PR与NF1之间更有效的协同作用,从而导致转录起始增强。缺乏定位核小体的突变型MMTV启动子在存在H1的情况下不会显示出增强的转录协同作用。PR的结合导致H1磷酸化,其在转录起始时离开启动子。因此,H1在MMTV启动子的调控中发挥着复杂而动态的作用。