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Genomic functions of developmental pluripotency associated factor 4 (Dppa4) in pluripotent stem cells and cancer.
- Source :
-
Stem cell research [Stem Cell Res] 2018 Aug; Vol. 31, pp. 83-94. Date of Electronic Publication: 2018 Jul 19. - Publication Year :
- 2018
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Abstract
- Developmental pluripotency associated factor 4 (Dppa4) is a highly specific marker of pluripotent cells, and is also overexpressed in certain cancers, but its function in either of these contexts is poorly understood. In this study, we use ChIP-Seq to identify Dppa4 binding genome-wide in three distinct cell types: mouse embryonic stem cells (mESC), embryonal carcinoma cells, and 3T3 fibroblasts ectopically expressing Dppa4. We find a core set of Dppa4 binding sites shared across cell types, and also a substantial number of sites unique to each cell type. Across cell types Dppa4 shows a preference for binding to regions with active chromatin signatures, and can influence chromatin modifications at target genes. In 3T3 fibroblasts with enforced Dppa4 expression, Dppa4 represses the cell cycle inhibitor Cdkn2c and activates Ets family transcription factor Etv4, leading to alterations in the cell cycle that likely contribute to the oncogenic phenotype. Dppa4 also directly regulates Etv4 in mESC but represses it in this context, and binds with Oct4 to a set of shared targets that are largely independent of Sox2 and Nanog, indicating that Dppa4 functions independently of the core pluripotency network in stem cells. Together these data provide novel insights into Dppa4 function in both pluripotent and oncogenic contexts.<br /> (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Subjects :
- 3T3 Cells
Adenovirus E1A Proteins genetics
Adenovirus E1A Proteins metabolism
Animals
Cell Proliferation physiology
Chromatin genetics
Chromatin metabolism
Cyclin-Dependent Kinase Inhibitor p18 genetics
Cyclin-Dependent Kinase Inhibitor p18 metabolism
Embryonal Carcinoma Stem Cells cytology
Embryonal Carcinoma Stem Cells metabolism
Gene Expression Regulation
Genomics methods
Humans
Mice
Nuclear Proteins metabolism
Pluripotent Stem Cells cytology
Pluripotent Stem Cells metabolism
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-ets genetics
Proto-Oncogene Proteins c-ets metabolism
Transfection
Embryonal Carcinoma Stem Cells physiology
Nuclear Proteins genetics
Pluripotent Stem Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1876-7753
- Volume :
- 31
- Database :
- MEDLINE
- Journal :
- Stem cell research
- Publication Type :
- Academic Journal
- Accession number :
- 30031967
- Full Text :
- https://doi.org/10.1016/j.scr.2018.07.009