A phosphomimetic mutation in the Sall1 repression motif disrupts recruitment of the nucleosome remodeling and deacetylase complex and repression of Gbx2
A phosphomimetic mutation in the Sall1 repression motif disrupts recruitment of the nucleosome remodeling and deacetylase complex and repression of Gbx2
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DOI：
10.1074/jbc.m703702200
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发表时间：
2007-11-30
影响因子：
4.8
通讯作者：
Rauchman, Michael
中科院分区：
文献类型：
--
作者：
Lauberth, Shannon M.;Bilyeu, Amy C.;Rauchman, Michael
多锌指转录因子Sall1是一个重要的发育调节因子，通过募集核小体重塑和脱乙酰酶（NuRD）复合物介导抑制。尽管Sall 1中的短保守肽基序足以招募NuRD，但其在体内调节天然Sall 1靶基因的能力尚未得到证实。在这份报告中，我们证明了在体内的Sall1抑制基序的作用，并描述了一种新的直接靶基因Sall1，Gbx2，这是直接抑制在一个NuRD依赖的方式。Sall1抑制Gbx2的能力在表达NuRD结合缺陷的Sall1突变形式的爪蟾胚胎中受损。最后，我们表明，蛋白激酶C磷酸化丝氨酸2的Sall1阻遏基序，并揭示了磷酸化的丝氨酸2突变破坏的能力Sall1阻遏Gbx2在细胞培养和非洲爪蟾胚胎。总之，这些研究确立了Sall1通过Sall1阻遏基序来介导天然靶基因的阻遏，并提出了一种模型，其中Sall1对基因表达的动态控制由Sall1阻遏基序的丝氨酸磷酸化来调节。
The multizinc finger transcription factor Sall1 is a critical developmental regulator that mediates repression through the recruitment of the nucleosome remodeling and deacetylase ( NuRD) complex. Although a short conserved peptide motif in Sall1 is sufficient to recruit NuRD, its ability to regulate native Sall1 target genes in vivo has not been demonstrated. In this report, we demonstrate an in vivo role for the Sall1 repression motif and describe a novel direct target gene of Sall1, Gbx2, that is directly repressed in a NuRD-dependent fashion. The ability of Sall1 to repress Gbx2 was impaired in Xenopus embryos expressing mutant forms of Sall1 that are defective for NuRD binding. Finally, we demonstrate that protein kinase C phosphorylates serine 2 of the Sall1 repression motif and reveal that a phosphomimetic mutation of serine 2 disrupts the ability of Sall1 to repress Gbx2 in cell culture and Xenopus embryos. Together, these studies establish that Sall1 recruits NuRD via the Sall1 repression motif to mediate repression of a native target gene and suggest a model in which dynamic control of gene expression by Sall1 is modulated by serine phosphorylation of the Sall1 repression motif.