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1.
Dev Biol ; 323(1): 41-52, 2008 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-18786525

RESUMO

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.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Proteína Wnt1/metabolismo , Adenosina Trifosfatases/genética , Animais , Células Cultivadas , Cromatina/metabolismo , Drosophila/citologia , Drosophila/genética , Drosophila/metabolismo , Drosophila/fisiologia , Proteínas de Drosophila/genética , Mutação , Ligação Proteica , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Transcrição Gênica , Proteína Wnt1/genética
2.
J Cell Sci ; 119(Pt 3): 395-402, 2006 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-16443747

RESUMO

Wnts are secreted proteins that are essential for a wide array of developmental and physiological processes. They signal across the plasma membrane by interacting with serpentine receptors of the Frizzled (Fz) family and members of the low-density-lipoprotein-related protein (LRP) family. Activation of Fz-LRP promotes the stability and nuclear localization of beta-catenin by compromising the ability of a multiprotein complex containing axin, adenomatosis polyposis coli (APC) and glycogen synthase kinase 3 (GSK3) to target it for degradation and block its nuclear import. The Fz-LRP receptor complex probably accomplishes this by generating multiple signals in the cytoplasm. These involve activation of Dishevelled (Dsh), possibly through trimeric G proteins and LRP-mediated axin binding and/or degradation. However, individual Wnts and Fzs can activate both beta-catenin-dependent and -independent pathways, and Fz co-receptors such as LRP probably provide some of this specificity. Additional, conflicting data concern the role of the atypical receptor tyrosine kinase Ryk, which might mediate Wnt signaling independently of Fz and/or function as a Fz co-receptor in some cells.


Assuntos
Transdução de Sinais/fisiologia , Proteínas Wnt/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Núcleo Celular/metabolismo , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Complexos Multiproteicos/metabolismo , Receptores de Neurotransmissores/metabolismo
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