The transcriptional activator ZNF143 is essential for normal development in zebrafish.

The transcriptional activator ZNF143 is essential for normal development in zebrafish.
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DOI:
10.1186/1471-2199-13-3
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发表时间:
2012-01-23
影响因子:
--
通讯作者:
Kunkel GR
Kunkel GR
中科院分区:
生物3区
文献类型:
--
作者:
Halbig KM;Lekven AC;Kunkel GR

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ZNF 143是一种序列特异性DNA结合蛋白,通过RNA聚合酶II或III刺激小RNA基因的转录,或通过RNA聚合酶II刺激蛋白质编码基因的转录,使用可分离的激活结构域。我们描述的表型效应敲低后,这种蛋白质在开发斑马鱼(斑马鱼)胚胎注射吗啉代反义寡核苷酸靶znf143 mRNA。功能丧失表型是多效性的,包括广泛的异常,包括心脏、血液、耳和中脑后脑边界的缺陷。通过共注射编码全长ZNF143蛋白的合成mRNA来挽救缺陷,但不通过缺乏氨基末端激活结构域的蛋白来挽救。因此,在敲低后,几个标记基因的表达受到影响,包括GATA结合蛋白1(gata1)、心肌肌球蛋白轻链2(cmlc2)和配对盒基因2a(pax2a)。斑马鱼pax2a基因近端启动子含有两个ZNF 143结合位点,在转染细胞中由该启动子驱动的报告基因转录被该蛋白激活。斑马鱼胚胎的正常发育需要ZNF 143。此外,pax2a基因可能是ZNF 143在斑马鱼发育过程中的许多蛋白质编码基因靶点之一。
ZNF143 is a sequence-specific DNA-binding protein that stimulates transcription of both small RNA genes by RNA polymerase II or III, or protein-coding genes by RNA polymerase II, using separable activating domains. We describe phenotypic effects following knockdown of this protein in developing Danio rerio (zebrafish) embryos by injection of morpholino antisense oligonucleotides that target znf143 mRNA. The loss of function phenotype is pleiotropic and includes a broad array of abnormalities including defects in heart, blood, ear and midbrain hindbrain boundary. Defects are rescued by coinjection of synthetic mRNA encoding full-length ZNF143 protein, but not by protein lacking the amino-terminal activation domains. Accordingly, expression of several marker genes is affected following knockdown, including GATA-binding protein 1 (gata1), cardiac myosin light chain 2 (cmlc2) and paired box gene 2a (pax2a). The zebrafish pax2a gene proximal promoter contains two binding sites for ZNF143, and reporter gene transcription driven by this promoter in transfected cells is activated by this protein. Normal development of zebrafish embryos requires ZNF143. Furthermore, the pax2a gene is probably one example of many protein-coding gene targets of ZNF143 during zebrafish development.
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