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ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Chinese Acad Agr Sci, Inst Anim Sci, Key Lab Farm Anim Genet Resources & Utilizat, Minist Agr China, Beijing, Peoples R China.
Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Ain Shams Univ, Dept Anim Prod, Cairo, Egypt.
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2019 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, no 1, p. 88-100Article in journal (Refereed) Published
Abstract [en]

Zinc finger BED domain containing protein 6 (Zbed6) has evolved from a domesticated DNA transposon and encodes a transcription factor unique to placental mammals. The aim of the present study was to investigate further the role of ZBED6 in insulin-producing cells, using mouse MIN6 cells, and to evaluate the effects of Zbed6 knockdown on basal -cell functions, such as morphology, transcriptional regulation, insulin content, and release. Zbed6-silenced cells and controls were characterized with a range of methods, including RNA sequencing, chromatin immunoprecipitation sequencing, insulin content and release, subplasma membrane Ca2+ measurements, cAMP determination, and morphologic studies. More than 700 genes showed differential expression in response to Zbed6 knockdown, which was paralleled by increased capacity to generate cAMP, as well as by augmented subplasmalemmal calcium concentration and insulin secretion in response to glucose stimulation. We identified >4000 putative ZBED6-binding sites in the MIN6 genome, with an enrichment of ZBED6 sites at upregulated genes, such as the -cell transcription factors v-maf musculoaponeurotic fibrosarcoma oncogene homolog A and Nk6 homeobox 1. We also observed altered morphology/growth patterns, as indicated by increased cell clustering, and in the appearance of axon-like Neurofilament, medium polypeptide and tubulin 3, class III-positive protrusions. We conclude that ZBED6 acts as a transcriptional regulator in MIN6 cells and that its activity suppresses insulin production, cell aggregation, and neuronal-like differentiation.Wang, X., Jiang, L., Wallerman, O., Younis, S., Yu, Q., Klaesson, A., Tengholm, A., Welsh, N., Andersson, L. ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells.

Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL , 2019. Vol. 33, no 1, p. 88-100
Keywords [en]
-cells, cell adhesion, transcriptome analysis, ChIP-seq
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-377365DOI: 10.1096/fj.201600835RISI: 000457401500007PubMedID: 29957057OAI: oai:DiVA.org:uu-377365DiVA, id: diva2:1289942
Funder
Swedish Research Council, 80576801Swedish Research Council, 70374401Swedish Research CouncilKnut and Alice Wallenberg FoundationSwedish Child Diabetes FoundationNovo NordiskErnfors FoundationSwedish Diabetes AssociationAvailable from: 2019-02-19 Created: 2019-02-19 Last updated: 2019-02-19Bibliographically approved

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Wang, XuanJiang, LinYounis, ShadyYu, QianKlaesson, AxelTengholm, AndersWelsh, NilsAndersson, Leif

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Wang, XuanJiang, LinYounis, ShadyYu, QianKlaesson, AxelTengholm, AndersWelsh, NilsAndersson, Leif
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Department of Medical Cell BiologyScience for Life Laboratory, SciLifeLabDepartment of Medical Biochemistry and Microbiology
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