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Effect of Th-POK deficiency on global gene expression in liver Va14i NKT cells

ABSTRACT: We sought to identify genes regulated by the transcription factor Th-POK (Zbtb7b) in liver Va14i NKT cells, by RNA microarray analysis of global gene expression in Va14i NKT cells from mice homozygous for the Th-POK-inactivating hd point mutation as compared with the same cell population isolated from heterozygous or wild-type age-matched mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE34179 | GEO | 2012/12/01

SECONDARY ACCESSION(S): PRJNA149691

REPOSITORIES: GEO

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Effect of Th-POK deficiency on global gene expression in liver Va14i NKT cells

Project description:We sought to identify genes regulated by the transcription factor Th-POK (Zbtb7b) in liver Va14i NKT cells, by RNA microarray analysis of global gene expression in Va14i NKT cells from mice homozygous for the Th-POK-inactivating hd point mutation as compared with the same cell population isolated from heterozygous or wild-type age-matched mice. Two sample set pairs of hd/hd and either hd/+ or +/+ age-matched Va14i NKT cells were prepared via magnetic selection and cell sorting, and total RNA prepared using a Qiagen Rneasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD.

2012-12-01 | E-GEOD-34179 | biostudies-arrayexpress

Gene expression in mammary glands of lactating wild-type or Th-POK-deficient mice.

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Project description:TET proteins mediate DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other oxidative derivatives. We have previously demonstrated a dynamic enrichment of 5hmC during T and invariant natural killer T cell lineage specification. Here, we investigate shared signatures in gene expression of Tet2/3 DKO CD4 single positive (SP) and iNKT cells in the thymus. We discover that TET proteins exert a fundamental role in regulating the expression of the lineage specifying factor Th-POK, which is encoded by Zbtb7b. We demonstrate that TET proteins mediate DNA demethylation - surrounding a proximal enhancer, critical for the intensity of Th-POK expression. In addition, TET proteins drive the DNA demethylation of site A at the Zbtb7b locus to facilitate GATA3 binding. GATA3 induces Th-POK expression in CD4 SP cells. Finally, by introducing a novel mouse model that lacks TET3 and expresses full length, catalytically inactive TET2, we establish a causal link between TET2 catalytic activity and lineage specification of both conventional and unconventional T cells.

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Mus musculus

Project description:Effect of Th-POK deficiency on global gene expression in liver Va14i NKT cells

| PRJNA149691 | ENA

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