Kimura Atsushi P, Liebhaber Stephen A, Cooke Nancy E
Departments of Genetics and Medicine, University of Pennsylvania, 752b Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Mol Endocrinol. 2004 Apr;18(4):1018-32. doi: 10.1210/me.2003-0468. Epub 2004 Jan 8.
Developmental control of eukaryotic gene expression is tightly linked to alterations in chromatin structure. Studies of the hGH multigene cluster suggest that the four placental genes are activated by a pathway of histone modification distinct from the pathway leading to activation of the single pituitary hGH-N gene. The relationship between histone acetylation and hGH-N activation in the pituitary has been previously defined using a combination of epigenetic mapping and transgenic analyses. The repeated gene structures within the hGH cluster had been an impediment to comparable analysis of placental gene activation. In the present report we defined patterns of core histone acetylation and methylation within and flanking the hGH cluster in human placental chromatin. These data highlight differences between placental and pituitary pathways of transcriptional control at the hGH cluster and suggest that selective activation of the placental genes reflects distinct roles for histone acetyltransferase and histone methyltransferase coactivator complexes.
真核基因表达的发育控制与染色质结构的改变紧密相关。对hGH多基因簇的研究表明，四个胎盘基因是通过一种组蛋白修饰途径被激活的，该途径不同于导致单个垂体hGH-N基因激活的途径。垂体中组蛋白乙酰化与hGH-N激活之间的关系先前已通过表观遗传图谱和转基因分析相结合的方法得以确定。hGH簇内重复的基因结构一直是对胎盘基因激活进行类似分析的障碍。在本报告中，我们确定了人胎盘染色质中hGH簇内部及其侧翼的核心组蛋白乙酰化和甲基化模式。这些数据突出了hGH簇在胎盘和垂体转录控制途径之间的差异，并表明胎盘基因的选择性激活反映了组蛋白乙酰转移酶和组蛋白甲基转移酶共激活复合物的不同作用。
