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Characteristic patterns of N oct-3 binding to a set of neuronal promoters.

机译:N oct-3与一组神经元启动子结合的特征模式。

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摘要

N Oct-3, a neurospecific POU protein, homodimerizes in a non-cooperative fashion on the neuronal aromatic l-amino acid decarboxylase gene promoter and generates heterodimers with HNF-3beta. Several other neuronal gene promoters, the corticotropin releasing hormone and the aldolase C gene promoters also contain overlapping binding sites for N Oct-3 and HNF-3beta. We have demonstrated that N Oct-3 presents a non-cooperative homodimerization on these two additional targets and can also give rise to heterodimers with HNF-3beta. Surprisingly, despite the high degree of conservation of the respective POU subunits, the ubiquitous POU protein Oct-1 can only form monomers even in the presence of either N Oct-3 or HNF-3beta on these DNA targets. Our data indicate that this difference is correlated with the specific ability of a portion of the N Oct-3 linker to fold as an alpha-helix, a property shared by class III POU proteins. These results suggest that this novel binding pattern permits the heterodimerization of N Oct-3 and HNF-3beta on the neuronal promoters, which could be a key issue in the development of the nervous system and possibly tumors of neural origin.
机译:N Oct-3是一种神经特异性的POU蛋白,在神经元芳香族1-氨基酸脱羧酶基因启动子上以非合作方式均二聚,并生成具有HNF-3beta的异二聚体。其他几个神经元基因启动子,促肾上腺皮质激素释放激素和醛缩酶C基因启动子也包含N Oct-3和HNF-3beta的重叠结合位点。我们已经证明,N Oct-3在这两个另外的靶标上存在非合作的均二聚化作用,并且还可能引起HNF-3beta异二聚体。出人意料的是,尽管各个POU亚基的高度保守,但普遍存在的POU蛋白Oct-1即使在这些DNA靶标上存在N Oct-3或HNF-3beta时也只能形成单体。我们的数据表明,这种差异与N Oct-3接头的一部分折叠成α-螺旋(一种由III类POU蛋白质共享的特性)的特异性能力相关。这些结果表明,这种新颖的结合模式允许N Oct-3和HNF-3beta在神经元启动子上异源二聚化,这可能是神经系统以及可能是神经源性肿瘤发展中的关键问题。

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