ACTIVATION OF SKELETAL ALPHA-ACTIN GENE-TRANSCRIPTION - THE COOPERATIVE FORMATION OF SERUM RESPONSE FACTOR-BINDING COMPLEXES OVER POSITIVE CIS-ACTING PROMOTER SERUM RESPONSE ELEMENTS DISPLACES A NEGATIVE-ACTING NUCLEAR FACTOR ENRICHED IN REPLICATING MYOBLASTS AND NONMYOGENIC CELLS
ACTIVATION OF SKELETAL ALPHA-ACTIN GENE-TRANSCRIPTION - THE COOPERATIVE FORMATION OF SERUM RESPONSE FACTOR-BINDING COMPLEXES OVER POSITIVE CIS-ACTING PROMOTER SERUM RESPONSE ELEMENTS DISPLACES A NEGATIVE-ACTING NUCLEAR FACTOR ENRICHED IN REPLICATING MYOBLASTS AND NONMYOGENIC CELLS
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DOI：
10.1128/mcb.11.10.5090
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发表时间：
1991-10-01
影响因子：
5.3
通讯作者：
SCHWARTZ, RJ
中科院分区：
文献类型：
--
作者：
LEE, TC;CHOW, KL;SCHWARTZ, RJ
禽类骨骼α-肌动蛋白基因的生肌细胞类型限制性表达需要三个uspstream CBAR顺式作用启动子元件，其含有血清反应元件(SRE)的内核CC(A/T)6GG(K.L.Chow和R.J.Schwartz，Mol.Cell.Biol.10：528-538，1990)。 这些肌动蛋白 SRE 元件与两种不同的核蛋白、血清反应因子 (SRF) 和此处描述的另一个因子 F-ACT1 显示出不同的结合特性。 SRF 能够以各种亲和力结合所有肌动蛋白 SRE。 这种多位点相互作用的特点是协同结合事件，因为两个高亲和力的近端和远端 SRE 促进了与 SRF 的弱中心位点相互作用，导致形成更高阶的 SRF 启动子复合物。 功能分析表明，不间断的多重 SRF-DNA 相互作用对于生肌细胞中的启动子活性至关重要。 F-ACT1 在非生肌细胞和复制性成肌细胞中的水平高于在肌管中的水平，仅与近端 SRE 结合，并且由于其碱基接触重叠，其结合与 SRF 的结合是相互排斥的。 然而，SRF 结合的协同启动子可以有效地取代预结合的 F-ACT1。 此外，完整的 F-ACT1 结合位点通过限制成肌细胞中的发育定时表达来充当负启动子元件。 因此，F-ACT1 可能充当骨骼 α-肌动蛋白基因转录的抑制因子。 F-ACT1 和 SRF 之间的相互作用可能构成调节肌节肌动蛋白基因表达的发育和生理调节机制。
Three uspstream CBAR cis-acting promoter elements, containing the inner core CC(A/T)6GG of the serum response element (SRE), are required for myogenic cell type-restricted expression of the avian skeletal alpha-actin gene (K. L. Chow and R. J. Schwartz, Mol. Cell. Biol. 10:528-538, 1990). These actin SRE elements display differential binding properties with two distinct nuclear proteins, serum response factor (SRF) and another factor described here as F-ACT1. SRF is able to bind to all actin SREs with various affinities. This multisite interaction is marked by cooperative binding events in that the two high-affinity proximal and distal SREs facilitate the weak central-site interaction with SRF, leading to the formation of a higher-order SRF-promoter complex. Functional analyses reveal that undisrupted multiple SRF-DNA interactions are absolutely essential for promoter activity in myogenic cells. F-ACT1, present at higher levels in nonmyogenic cells and replicating myoblasts than in myotubes, binds solely to the proximal SRE, and its binding is mutually exclusive with that of SRF owing to their overlapping base contacts. The cooperative promoter binding by SRF, however, can effectively displace prebound F-ACT1. In addition, an intact F-ACT1 binding site acts as a negative promoter element by restricting developmentally timed expression in myoblasts. F-ACT1 may therefore act as a repressor of skeletal alpha-actin gene transcription. This interplay between F-ACT1 and SRF may constitute a developmental as well as a physiologically regulated mechanism which modulates sarcomeric actin gene expression.