Genomic functions of developmental pluripotency associated factor 4 (Dppa4) in pluripotent stem cells and cancer.

Stem Cell Research
Rachel Herndon KleinPaul S Knoepfler

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 da...Continue Reading

Citations

Jan 30, 2019·Genes & Development·Mélanie Eckersley-MaslinWolf Reik
Jun 24, 2020·Nature Structural & Molecular Biology·Mélanie A Eckersley-MaslinWolf Reik
Dec 19, 2020·Biochemical Society Transactions·Mélanie A Eckersley-Maslin
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Maxim V C Greenberg

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Datasets Mentioned

BETA
GSE95055
GSE58709

Methods Mentioned

BETA
ChIP-Seq
immunoprecipitation
transfection
flow cytometry
co-IP
histone acetylation

Software Mentioned

MACS
DAVID
Cistrome
BWA
Galaxy
Burrows Aligner ( BWA )

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