Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes

Abstract Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters...

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Autores principales:	Praveena L. Ramanujam, Sonam Mehrotra, Ram Parikshan Kumar, Shreekant Verma, Girish Deshpande, Rakesh K. Mishra, Sanjeev Galande
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a6256373306449cabbc38a6ba62c5edf
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spelling	oai:doaj.org-article:a6256373306449cabbc38a6ba62c5edf2021-12-02T14:11:31ZGlobal chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes10.1038/s41598-021-81324-22045-2322https://doaj.org/article/a6256373306449cabbc38a6ba62c5edf2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81324-2https://doaj.org/toc/2045-2322Abstract Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.Praveena L. RamanujamSonam MehrotraRam Parikshan KumarShreekant VermaGirish DeshpandeRakesh K. MishraSanjeev GalandeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Praveena L. Ramanujam Sonam Mehrotra Ram Parikshan Kumar Shreekant Verma Girish Deshpande Rakesh K. Mishra Sanjeev Galande Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
description	Abstract Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.
format	article
author	Praveena L. Ramanujam Sonam Mehrotra Ram Parikshan Kumar Shreekant Verma Girish Deshpande Rakesh K. Mishra Sanjeev Galande
author_facet	Praveena L. Ramanujam Sonam Mehrotra Ram Parikshan Kumar Shreekant Verma Girish Deshpande Rakesh K. Mishra Sanjeev Galande
author_sort	Praveena L. Ramanujam
title	Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
title_short	Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
title_full	Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
title_fullStr	Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
title_full_unstemmed	Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
title_sort	global chromatin organizer satb1 acts as a context-dependent regulator of the wnt/wg target genes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a6256373306449cabbc38a6ba62c5edf
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Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes

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