High throughput genomic screen identifies multiple factors that promote cooperative Wnt signaling.

High throughput genomic screen identifies multiple factors that promote cooperative Wnt signaling.
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DOI:
10.1371/journal.pone.0055782
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Morrisey EE
Morrisey EE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miller MF;Cohen ED;Baggs JE;Hogenesch JB;Morrisey EE

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先前的研究表明,某些 Wnt 配体可以以细胞类型特异性方式促进高水平的协同信号传导。为了探索这种协同 Wnt 信号传导的潜在机制,我们对 14,000 多个 cDNA 进行了高通量筛选,以确定在单一 Wnt 配体 Wnt2 的背景下促进协同 Wnt 信号传导的基因。除了已知促进 Wnt 信号传导的其他因子(包括 Pias4)之外,该筛选还鉴定了几个同源盒因子,包括 Msx2、Nkx5.2 和 Esx1。 Msx2 显性活性或显性失活形式的产生表明同源盒因子协同促进 Wnt 信号传导的机制是通过它们抑制基因转录的能力。这些数据确定了广泛的同源框代码,该代码通过转录抑制来增强 Wnt 信号传导。
Previous studies have demonstrated that certain Wnt ligands can promote high levels of cooperative signaling in a cell type specific manner. To explore the underlying mechanism of this cooperative Wnt signaling, we performed a high-throughput screen of more than 14,000 cDNAs to identify genes that promote cooperative Wnt signaling in the context of a single Wnt ligand, Wnt2. This screen identified several homeobox factors including Msx2, Nkx5.2, and Esx1, in addition to other factors known to promote Wnt signaling including Pias4. Generation of dominant-active or dominant-negative forms of Msx2 indicate that the mechanism by which homeobox factors cooperatively promote Wnt signaling is through their ability to repress gene transcription. These data identify a broad homeobox code, which acts to increase Wnt signaling through transcriptional repression.
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