Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.

Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15(Ink4)) or Cdkn1a (p21(Cip1)). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1...

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Autores principales:	Adrián Sanz-Moreno, David Fuhrmann, Elmar Wolf, Björn von Eyss, Martin Eilers, Hans-Peter Elsässer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e17306d611d94d25bdfbb88de2606a0b
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spelling	oai:doaj.org-article:e17306d611d94d25bdfbb88de2606a0b2021-11-18T08:31:58ZMiz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.1932-620310.1371/journal.pone.0089187https://doaj.org/article/e17306d611d94d25bdfbb88de2606a0b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586582/?tool=EBIhttps://doaj.org/toc/1932-6203Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15(Ink4)) or Cdkn1a (p21(Cip1)). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11 cells. Further analysis revealed decreased Stat5 activity in Miz1ΔPOZ mammary glands and an attenuated expression of Stat5 targets. Gene expression of the Prolactin receptor (PrlR) and ErbB4, both critical for Stat5 phosphorylation (pStat5) or pStat5 nuclear translocation, was decreased in Miz1ΔPOZ females. Microarray, ChIP-Seq and gene set enrichment analysis revealed a down-regulation of Miz1 target genes being involved in vesicular transport processes. Our data suggest that deranged intracellular transport and localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant glands and cause the observed lactation phenotype.Adrián Sanz-MorenoDavid FuhrmannElmar WolfBjörn von EyssMartin EilersHans-Peter ElsässerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89187 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adrián Sanz-Moreno David Fuhrmann Elmar Wolf Björn von Eyss Martin Eilers Hans-Peter Elsässer Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.
description	Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15(Ink4)) or Cdkn1a (p21(Cip1)). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11 cells. Further analysis revealed decreased Stat5 activity in Miz1ΔPOZ mammary glands and an attenuated expression of Stat5 targets. Gene expression of the Prolactin receptor (PrlR) and ErbB4, both critical for Stat5 phosphorylation (pStat5) or pStat5 nuclear translocation, was decreased in Miz1ΔPOZ females. Microarray, ChIP-Seq and gene set enrichment analysis revealed a down-regulation of Miz1 target genes being involved in vesicular transport processes. Our data suggest that deranged intracellular transport and localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant glands and cause the observed lactation phenotype.
format	article
author	Adrián Sanz-Moreno David Fuhrmann Elmar Wolf Björn von Eyss Martin Eilers Hans-Peter Elsässer
author_facet	Adrián Sanz-Moreno David Fuhrmann Elmar Wolf Björn von Eyss Martin Eilers Hans-Peter Elsässer
author_sort	Adrián Sanz-Moreno
title	Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.
title_short	Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.
title_full	Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.
title_fullStr	Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.
title_full_unstemmed	Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.
title_sort	miz1 deficiency in the mammary gland causes a lactation defect by attenuated stat5 expression and phosphorylation.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e17306d611d94d25bdfbb88de2606a0b
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Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.

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