Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing
Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing
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DOI：
10.1101/gr.086496.108
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发表时间：
2009-04-01
期刊：
影响因子：
7
通讯作者：
Larionov, Vladimir
中科院分区：
文献类型：
--
作者：
Kim, Jung-Hyun;Ebersole, Thomas;Larionov, Vladimir
围绕着丝粒区重复DNA序列对着丝粒/异染色质结构和功能的作用了解甚少。在这里，我们使用小鼠红白血病细胞（MEL）系统来研究重复DNA如何假设或组装成不同的染色质结构。我们表明，人类γ -卫星DNA阵列允许在邻近的转基因中转录允许的染色质构象，并有效地保护它免受表观遗传沉默。这些数组包含CTCF和Ikaros结合位点。在MEL细胞中，这种γ卫星DNA活性依赖于沿造血途径参与分化的Ikaros蛋白的结合。鉴于我们在大多数人类染色体的中心点周围区域发现了伽玛卫星DNA，以及伽玛卫星阵列在其自然位置上的动态染色质状态，我们认为伽玛卫星DNA代表了功能性着丝粒的一个独特区域，可能在防止异染色质扩散到中心点周围区域之外发挥作用。
The role of repetitive DNA sequences in pericentromeric regions with respect to kinetochore/heterochromatin structure and function is poorly understood. Here, we use a mouse erythroleukemia cell (MEL) system for studying how repetitive DNA assumes or is assembled into different chromatin structures. We show that human gamma-satellite DNA arrays allow a transcriptionally permissive chromatin conformation in an adjacent transgene and efficiently protect it from epigenetic silencing. These arrays contain CTCF and Ikaros binding sites. In MEL cells, this gamma-satellite DNA activity depends on binding of Ikaros proteins involved in differentiation along the hematopoietic pathway. Given our discovery of gamma-satellite DNA in pericentromeric regions of most human chromosomes and a dynamic chromatin state of gamma-satellite arrays in their natural location, we suggest that gamma-satellite DNA represents a unique region of the functional centromere with a possible role in preventing heterochromatin spreading beyond the pericentromeric region.