Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of imprint free mouse mouse embryonic stem (IF-ES) cells vs wild type MEFs

ABSTRACT: Loss of imprinting (LOI), commonly observed in human tumors, refers to loss of monoallelic gene regulation normally conferred by parent-of-origin specific DNA methylation. To test the function of LOI in tumorigenesis, we developed a model using transient demethylation to generate imprint-free mouse embryonic stem (IF-ES) cells. To analyse the effect of LOI on gene expression, we compared gene expression profiles from embryonic fibroblasts derived from IF-ES cells (IF-MEFs) and wildtype MEFs.

INSTRUMENT(S): GenePix 4000B [Axon Instruments]

ORGANISM(S): Mus musculus

SUBMITTER: Tobias Brambrink

PROVIDER: E-MEXP-450 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Global loss of imprinting leads to widespread tumorigenesis in adult mice.

Holm Teresa M TM Jackson-Grusby Laurie L Brambrink Tobias T Yamada Yasuhiro Y Rideout William M WM Jaenisch Rudolf R

Cancer cell 20051001 4

Loss of imprinting (LOI), commonly observed in human tumors, refers to loss of monoallelic gene regulation normally conferred by parent-of-origin-specific DNA methylation. To test the function of LOI in tumorigenesis, we developed a model by using transient demethylation to generate imprint-free mouse embryonic stem cells (IF-ES cells). Embryonic fibroblasts derived from IF-ES cells (IF-MEFs) display TGFbeta resistance and reduced p19 and p53 expression and form tumors in SCID mice. IF-MEFs exhi ...[more]

PMID: 16226703

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Project description:Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins). Abstract (submitted paper): rationale for expression profiling Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic developmentâbecause Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferationâexplained in part by impaired cell cycle progression as well as increased apoptosisâand terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesisâsuch as alpha-globin and mitoferrin 1âdemonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

Dataset Information

Transcription profiling of imprint free mouse mouse embryonic stem (IF-ES) cells vs wild type MEFs

Publications

Global loss of imprinting leads to widespread tumorigenesis in adult mice.

Similar Datasets

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