The chromatin remodelers ISWI and ACF1 directly repress Wingless transcriptional targets
The chromatin remodelers ISWI and ACF1 directly repress Wingless transcriptional targets
复制标题
DOI：
10.1016/j.ydbio.2008.08.011
复制
发表时间：
2008-11-01
影响因子：
2.7
通讯作者：
Cadigan, Ken M.
中科院分区：
文献类型：
--
作者：
Liu, Yan I.;Chang, Mikyung V.;Cadigan, Ken M.
高度保守的Wingless/Wnt信号通路通过调节靶基因的表达来控制许多发育过程，最常见的是通过DNA结合蛋白的TCF家族成员。在缺乏信号传导的情况下，这些靶点中的许多被沉默，其机制涉及尚未完全理解的TCF。在这里，我们报告说，染色质重塑蛋白ISWI和ACF 1所需的基础上抑制果蝇WG靶基因。这种调节不是由于ISWI和ACF 1的全局抑制，并且与先前报道的它们在染色质组装中的作用不同。虽然ISWI定位于与TCF相同的Wingless靶基因染色质区域，但我们发现ACF 1与靶位点的结合更广泛。ACF 1的这种广泛分布依赖于ISWI，ISWI和ACF 1是TCF与染色质结合所必需的，同时还观察到ISWI-ACF 1在抑制Wingless靶标中的TCF独立作用。最后，我们表明，Wingless信号减少ACF 1结合WG的目标，和ISWI和ACF 1调节阻遏拮抗组蛋白H4乙酰化。我们的研究结果表明，WG信号激活靶基因的表达，部分是通过克服ISWI和ACF 1（C）2008 Elsevier Inc.维持的染色质屏障。All rights reserved.
The highly conserved Wingless/Wnt signaling pathway controls many developmental processes by regulating the expression of target genes, most often through members of the TCF family of DNA-binding proteins. In the absence of signaling, many of these targets are silenced, by mechanisms involving TCFs that are not fully understood. Here we report that the chromatin remodeling proteins ISWI and ACF1 are required for basal repression of WG target genes in Drosophila. This regulation is not due to global repression by ISWI and ACF1 and is distinct from their previously reported role in chromatin assembly. While ISWI is localized to the same regions of Wingless target gene chromatin as TCF, we find that ACF1 binds much more broadly to target loci. This broad distribution of ACF1 is dependent on ISWI ISWI and ACF1 are required for TCF binding to chromatin, while a TCF-independent role of ISWI-ACF1 in repression of Wingless targets is also observed. Finally, we show that Wingless signaling reduces ACF1 binding to WG targets, and ISWI and ACF1 regulate repression by antagonizing histone H4 acetylation. Our results argue that WG signaling activates target gene expression partly by overcoming the chromatin barrier maintained by ISWI and ACF1 (C) 2008 Elsevier Inc. All rights reserved.