Intramolecular control of transcriptional activity by the NK2-specific domain in NK-2 homeodomain proteins
Intramolecular control of transcriptional activity by the NK2-specific domain in NK-2 homeodomain proteins
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DOI：
10.1073/pnas.97.17.9443
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发表时间：
2000-08-15
影响因子：
11.1
通讯作者：
German, MS
中科院分区：
文献类型：
--
作者：
Watada, H;Mirmira, RG;German, MS
The developmentally important homeodomain transcription factors of the NK-2 class contain a highly conserved region, the NK2-specific domain (NK2-SD), The function of this domain, however, remains unknown. The primary structure of the NK2-SD suggests that it might function as an accessory DNA-binding domain or as a protein-protein interaction interface. To assess the possibility that the NK2-SD may contribute to DNA-binding specificity, we used a PCR-based approach to identify a consensus DNA-binding sequences for Nkx2.2, an NK-2 family member involved in pancreas and central nervous system development. The consensus sequence (T(C)(T)AAGT(GG)(AC)TT) is similar to the known binding sequences for other NK-2 homeodomain proteins, but we show that the NK2-SD does not contribute significantly to specific DNA binding to this sequence. To determine whether the NK2-SD contributes to transactivation, we used GAL4-Nkx2.2 fusion constructs to map a powerful transcriptional activation domain in the C-terminal region beyond the conserved NK2-SD. interestingly, this C-terminal region functions as a transcriptional activator only in the absence of an intact NK2-SD, The NK2-SD also can mask transactivation from the paired homeodomain transcription factor Pax6, but it has no effect on transcription by itself, These results demonstrate that the NK2-SD functions as an intramolecular regulator of the C-terminal activation domain in Nkx2.2 and support a model in which interactions through the NK2-SD regulate the ability of NK-2-class proteins to activate specific genes during development.
