Mouse homolog of SALL1, a causative gene for Townes-Brocks syndrome, binds to A/T-rich sequences in pericentric heterochromatin via its C-terminal zinc finger domains
Mouse homolog of SALL1, a causative gene for Townes-Brocks syndrome, binds to A/T-rich sequences in pericentric heterochromatin via its C-terminal zinc finger domains
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DOI：
10.1111/j.1365-2443.2007.01042.x
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发表时间：
2007-02-01
期刊：
影响因子：
2.1
通讯作者：
Nishinakamura, Ryuichi
中科院分区：
文献类型：
--
作者：
Yamashita, Kazunari;Sato, Akira;Nishinakamura, Ryuichi
Spalt（sal）基因家族从果蝇到人类都是保守的。人类SALL 1基因突变导致Townes-Brocks综合征，其特征是耳、四肢、肛门、肾脏和心脏异常。Sall 1是SALL 1的鼠同源物，对于肾脏形成是必需的，并且Sall 1和SALL 1都定位于细胞核中的异染色质。在这里，我们提出了一个异染色质定位的Sall 1的分子机制。突变分析表明，第7 - 10位的C-末端双锌指基序的定位所需的。一种最C端双锌指（第9 - 10位）结合特定A/T富集序列的重组蛋白。此外，Sall 1与异染色质中的主要卫星DNA的富含A/T的序列相关。因此，Sall 1可以通过其C-末端双锌指与主要卫星DNA的富含A/T的序列结合，从而介导其定位于异染色质。
The Spalt (sal) gene family is conserved from Drosophila to humans. Mutations of human SALL1 cause Townes-Brocks syndrome, with features of ear, limb, anal, renal and heart anomalies. Sall1, a murine homolog of SALL1, is essential for kidney formation, and both Sall1 and SALL1 localize to heterochromatin in the nucleus. Here, we present a molecular mechanism for the heterochromatin localization of Sall1. Mutation analyses revealed that the 7th-10th C-terminal double zinc finger motifs were required for the localization. A recombinant protein of the most C-terminal double zinc finger (9th-10th) bound to specific A/T-rich sequences. Furthermore, Sall1 associated with A/T-rich sequences of the major satellite DNA in heterochromatin. Thus Sall1 may bind to A/T-rich sequences of the major satellite DNA via its C-terminal double zinc fingers, thereby mediating its localization to heterochromatin.