SALL1的小鼠同源物是Townes-Brocks综合征的致病基因，它通过其C端锌指结构域与着丝粒周围异染色质中的富含A/T的序列结合。

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.

作者信息

Yamashita Kazunari, Sato Akira, Asashima Makoto, Wang Pi-Chao, Nishinakamura Ryuichi

机构信息

Division of Integrative Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

出版信息

Genes Cells. 2007 Feb;12(2):171-82. doi: 10.1111/j.1365-2443.2007.01042.x.

DOI:10.1111/j.1365-2443.2007.01042.x

PMID:17295837

Abstract

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.

摘要

Spalt（sal）基因家族从果蝇到人类都是保守的。人类SALL1的突变会导致汤姆斯-布罗克斯综合征，其特征为耳、肢体、肛门、肾脏和心脏异常。Sall1是SALL1的小鼠同源物，对肾脏形成至关重要，并且Sall1和SALL1都定位于细胞核中的异染色质。在此，我们提出了Sall1异染色质定位的分子机制。突变分析表明，第7至10个C末端双锌指基序是定位所必需的。最末端的双锌指（第9至10个）的重组蛋白与特定的富含A/T的序列结合。此外，Sall1与异染色质中主要卫星DNA的富含A/T的序列相关。因此，Sall1可能通过其C末端双锌指与主要卫星DNA的富含A/T的序列结合，从而介导其向异染色质的定位。