The imprinting mechanism of the Prader–Willi/Angelman regional control center
The imprinting mechanism of the Prader–Willi/Angelman regional control center
复制标题
Prader-Willi/Angelman区域控制中心的印记机制
作者：
Jonathan Perk;Kirill Makedonski;L. Lande;H. Cedar;A. Razin;R. Shemer
染色体15 q11-q13上的2 Mb结构域携带涉及Prader-Willi（PWS）和Angelman（AS）综合征的印记基因，该结构域受印记中心的控制，该印记中心包括两个调节区，位于SNRPN启动子周围的PWS-SRO和位于上游35 kb的AS-SRO。在这里，我们描述了这两个序列及其相互作用的表观遗传特征的分析结果。AS-SRO对DNA酶I敏感，并且仅在母体等位基因上包装有乙酰化组蛋白H4和甲基化组蛋白H3（K4），并且这种印记的表观遗传结构在分裂细胞中保持，尽管没有明确的差异DNA甲基化。遗传分析表明，母体AS-SRO对于建立邻近PWS-SRO的DNA甲基化状态和闭合染色质结构至关重要。相反，PWS-SRO对AS-SRO的表观遗传特征没有影响。这些结果表明了一个逐步的、单向的程序，其中AS-SRO处的结构印记引起了母体PWS-SRO的等位基因特异性抑制，从而阻止了该等位基因上基因的区域激活。
The 2 Mb domain on chromosome 15q11–q13 that carries the imprinted genes involved in Prader–Willi (PWS) and Angelman (AS) syndromes is under the control of an imprinting center comprising two regulatory regions, the PWS‐SRO located around the SNRPN promoter and the AS‐SRO located 35 kb upstream. Here we describe the results of an analysis of the epigenetic features of these two sequences and their interaction. The AS‐SRO is sensitive to DNase I, and packaged with acetylated histone H4 and methylated histone H3(K4) only on the maternal allele, and this imprinted epigenetic structure is maintained in dividing cells despite the absence of clearcut differential DNA methylation. Genetic analysis shows that the maternal AS‐SRO is essential for setting up the DNA methylation state and closed chromatin structure of the neighboring PWS‐SRO. In contrast, the PWS‐SRO has no influence on the epigenetic features of the AS‐SRO. These results suggest a stepwise, unidirectional program in which structural imprinting at the AS‐SRO brings about allele‐specific repression of the maternal PWS‐SRO, thereby preventing regional activation of genes on this allele.
影响因子：
4.4
作者：
Davis, TL;Trasler, JM;Bartolomei, MS
通讯作者：
Bartolomei, MS
影响因子：
11.4
作者：
SELIG, S;OKUMURA, K;CEDAR, H
通讯作者：
CEDAR, H