Goren Alon, Tabib Amalia, Hecht Merav, Cedar Howard
Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel.
Genes Dev. 2008 May 15;22(10):1319-24. doi: 10.1101/gad.468308. Epub 2008 Apr 28.
The human beta-globin genes constitute a large chromosomal domain that is developmentally regulated. In nonerythroid cells, these genes replicate late in S phase, while in erythroid cells, replication is early. The replication origin is packaged with acetylated histones in erythroid cells, yet is associated with deacetylated histones in nonerythroid cells. Recruitment of histone acetylases to this origin brings about a transcription-independent shift to early replication in lymphocytes. In contrast, tethering of a histone deacetylase in erythroblasts causes a shift to late replication. These results suggest that histone modification at the origin serves as a binary switch for controlling replication timing.
人类β-珠蛋白基因构成一个受发育调控的大型染色体结构域。在非红细胞系细胞中,这些基因在S期晚期复制,而在红细胞系细胞中,复制较早。复制起点在红细胞系细胞中与乙酰化组蛋白结合,而在非红细胞系细胞中与去乙酰化组蛋白相关联。将组蛋白乙酰转移酶招募到这个起点会导致淋巴细胞中出现不依赖转录的向早期复制的转变。相反,在成红细胞中拴系组蛋白脱乙酰酶会导致向晚期复制的转变。这些结果表明,起点处的组蛋白修饰作为控制复制时间的二元开关。