Treacy M N, Neilson L I, Turner E E, He X, Rosenfeld M G
Eukaryotic Regulatory Biology Program, University of California, San Diego School of Medicine, La Jolla 92093-0648.
Cell. 1992 Feb 7;68(3):491-505. doi: 10.1016/0092-8674(92)90186-g.
I-POU, a POU domain nuclear protein that lacks two conserved basic amino acids of the POU homeodomain is coexpressed in the developing Drosophila nervous system with a second POU domain transcription factor, Cf1-a. I-POU does not bind to DNA but forms a POU domain-mediated, high affinity heterodimer with Cf1-a, inhibiting its ability to bind and activate the dopa decarboxylase gene. The I-POU/Cf1-a dimerization interface encompasses only the N-terminal basic region and helices 1 and 2 of the POU homeodomains with precise amino acid and alpha-helical requirements. twin of I-POU, an alternatively spliced transcript of the I-POU gene, encodes a protein containing the two basic amino acid residues absent in I-POU. Twin of I-POU is incapable of dimerizing with Cf1-a, but can act as a positive transcription factor on targets distinct from those regulated by Cf1-a. These findings suggest that the I-POU genomic locus simultaneously generates both a specific activator and inhibitor of gene transcription, capable of modulating two distinct regulatory programs during neural development.
I-POU是一种POU结构域核蛋白，它缺少POU同源结构域的两个保守碱性氨基酸，在发育中的果蝇神经系统中与另一种POU结构域转录因子Cf1-a共表达。I-POU不与DNA结合，但与Cf1-a形成POU结构域介导的高亲和力异二聚体，抑制其结合和激活多巴脱羧酶基因的能力。I-POU/Cf1-a二聚化界面仅包含POU同源结构域的N端碱性区域以及螺旋1和螺旋2，对氨基酸和α螺旋有精确要求。I-POU的孪生基因是I-POU基因的可变剪接转录本，编码一种包含I-POU中缺失的两个碱性氨基酸残基的蛋白质。I-POU的孪生基因不能与Cf1-a二聚化，但可作为一种正转录因子作用于与Cf1-a调控的靶标不同的靶标。这些发现表明，I-POU基因组位点同时产生基因转录的特异性激活剂和抑制剂，能够在神经发育过程中调节两种不同的调控程序。
