The Role of PTIP in Maintaining Embryonic Stem Cell Pluripotency

Pax transactivation domain‐interacting protein (PTIP) is a ubiquitously expressed, nuclear protein that is part of a histone H3K4 methyltransferase complex and is essential for embryonic development. Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in e...

Full description

Saved in:
Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2009-07, Vol.27 (7), p.1516-1523
Main Authors: Kim, Doyeob, Patel, Sanjeevkumar R., Xiao, Hong, Dressler, Gregory R.
Format: Article
Language:English
Subjects:
Animals
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - physiology
Blotting, Western
Carrier Proteins - genetics
Carrier Proteins - physiology
Cell Differentiation
Cells, Cultured
Chromatin Immunoprecipitation
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Epigenetics
Female
Histones - metabolism
Immunohistochemistry
Male
Methylation
Mice
Mice, Mutant Strains
Nuclear Proteins - genetics
Nuclear Proteins - physiology
Oct4
Octamer Transcription Factor-3 - genetics
Octamer Transcription Factor-3 - physiology
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
PTIP
Reverse Transcriptase Polymerase Chain Reaction
Spontaneous differentiation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pax transactivation domain‐interacting protein (PTIP) is a ubiquitously expressed, nuclear protein that is part of a histone H3K4 methyltransferase complex and is essential for embryonic development. Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in embryonic stem (ES) cells and, together with H3K27 methylation, constitutes a bivalent epigenetic signature. To address the function of PTIP in ES cells, we generated ES cell lines from a floxed ptip allele and deleted PTIP function with Cre recombinase. The ptip−/− ES cell lines exhibited a high degree of spontaneous differentiation to trophectoderm and a loss of pluripotency. Reduced levels of Oct4 expression and H3K4 methylation were observed. Upon differentiation, ptip−/− embryoid bodies showed reduced levels of marker gene expression for all three primary germ layers. These results suggest that the maintenance of H3K4 methylation is essential and requires PTIP function during the in vitro propagation of pluripotent ES cells. STEM CELLS 2009;27:1516–1523
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.79