Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology Hellas, 70013 Heraklio, Crete, Greece.
J Biol Chem. 2011 Jan 14;286(2):1037-45. doi: 10.1074/jbc.M110.170050. Epub 2010 Nov 9.
Sall1 is a multi-zinc finger transcription factor that regulates kidney organogenesis. It is considered to be a transcriptional repressor, preferentially localized on heterochromatin. Mutations or deletions of the human SALL1 gene are associated with the Townes-Brocks syndrome. Despite its high expression, no function was yet assigned for Sall1 in embryonic stem (ES) cells. In the present study, we show that Sall1 is expressed in a differentiation-dependent manner and physically interacts with Nanog and Sox2, two components of the core pluripotency network. Genome-wide mapping of Sall1-binding loci has identified 591 genes, 80% of which are also targeted by Nanog. A large proportion of these genes are related to self-renewal and differentiation. Sall1 positively regulates and synergizes with Nanog for gene transcriptional regulation. In addition, our data show that Sall1 suppresses the ectodermal and mesodermal differentiation. Specifically, the induction of the gastrulation markers T brachyury, Goosecoid, and Dkk1 and the neuroectodermal markers Otx2 and Hand1 was inhibited by Sall1 overexpression during embryoid body differentiation. These data demonstrate a novel role for Sall1 as a member of the transcriptional network that regulates stem cell pluripotency.
Sall1 是一种多锌指转录因子，可调节肾脏器官发生。它被认为是一种转录抑制因子，优先定位于异染色质上。人类 SALL1 基因突变或缺失与 Townes-Brocks 综合征有关。尽管 Sall1 表达水平很高，但在胚胎干细胞（ES 细胞）中尚未确定其功能。在本研究中，我们表明 Sall1 以分化依赖的方式表达，并与 Nanog 和 Sox2 发生物理相互作用，Nanog 和 Sox2 是核心多能性网络的两个组成部分。Sall1 结合位点的全基因组作图鉴定出 591 个基因，其中 80%的基因也被 Nanog 靶向。这些基因的很大一部分与自我更新和分化有关。Sall1 正向调节并与 Nanog 协同作用，调节基因转录调控。此外，我们的数据表明 Sall1 抑制外胚层和中胚层分化。具体而言，Sall1 的过表达在类胚体分化过程中抑制了原肠胚标志基因 T brachyury、Goosecoid 和 Dkk1 以及神经外胚层标志基因 Otx2 和 Hand1 的诱导。这些数据表明 Sall1 作为调节干细胞多能性的转录网络的成员具有新的作用。
