Grigoryev Sergei A, Nikitina Tatiana, Pehrson John R, Singh Prim B, Woodcock Christopher L
Department of Biochemistry and Molecular Biology, Penn State University College of Medicine, Hershey, PA 17033, USA.
J Cell Sci. 2004 Dec 1;117(Pt 25):6153-62. doi: 10.1242/jcs.01537.
Quiescent lymphocytes have small nuclei, filled with masses of facultative heterochromatin. Upon receiving mitogenic signals, these cells undergo nuclear enlargement, chromatin decondensation, the reactivation of cell proliferation, and changes in the intranuclear positioning of key genes. We examined the levels and intranuclear localization of major histone modifications and non-histone heterochromatin proteins in quiescent and reactivated mouse spleen lymphocytes. Dramatic and selective changes in localization of two heterochromatin-associated proteins, the histone variant macroH2A and HP1alpha occurred during lymphocyte reactivation. Reciprocal changes in the locations of these two proteins were observed in activated lymphocytes and cultured mouse fibroblasts induced into quiescence. We also describe a new apocentric nuclear compartment with a unique set of histone modifications that occurs as a zone of chromatin surrounding centromeric heterochromatin in differentiated lymphocytes. It is within this zone that the most significant changes occur in the transition from proliferation to quiescence. Our results suggest that constitutive centromeric heterochromatin plays an active role in cell differentiation and reactivation.
静止淋巴细胞的细胞核较小，充满了大量兼性异染色质。在接收到促有丝分裂信号后，这些细胞会经历细胞核增大、染色质解聚、细胞增殖重新激活以及关键基因在细胞核内定位的变化。我们检测了静止和重新激活的小鼠脾淋巴细胞中主要组蛋白修饰和非组蛋白异染色质蛋白的水平及细胞核内定位。在淋巴细胞重新激活过程中，两种与异染色质相关的蛋白，即组蛋白变体macroH2A和HP1α的定位发生了显著且选择性的变化。在活化淋巴细胞和诱导进入静止状态的培养小鼠成纤维细胞中观察到了这两种蛋白位置的相互变化。我们还描述了一种新的离中心核区室，其具有一组独特的组蛋白修饰，在分化淋巴细胞中作为围绕着着丝粒异染色质的染色质区域出现。正是在这个区域，从增殖到静止的转变过程中发生了最显著的变化。我们的结果表明，组成型着丝粒异染色质在细胞分化和重新激活中发挥着积极作用。
