Global gene expression changes between PTIP KO and control PerC B-1a cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE98402 | GEO | 2017/05/02
SECONDARY ACCESSION(S): PRJNA385000
REPOSITORIES: GEO
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Project description:PPARg and C/EBPa cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARg and C/EBPa expression during adipogenesis remain largely unclear. Here we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARg and C/EBPa expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARg expression and PPARg-stimulated C/EBPα expression. Further, PTIP is essential for induction of PPARg and C/EBPa expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARg and C/EBPa promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Furthermore, rescue of the adipogenesis defect in PTIP-/- MEFs requires co-expression of PPARg and C/EBPa. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight in mice. Thus, by regulating PPARg and C/EBPa expression, PTIP plays a critical role in adipogenesis. To identify PTIP-regulated genes, immortalized PTIP conditional knockout PTIPflox/flox MEFs were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PTIP+/+ or PTIP-/-) for 4 affymetrix microarrays.
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