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Series GSE8855 Query DataSets for GSE8855
Status Public on Sep 07, 2007
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by genome tiling array
Summary The recent discovery of a large number of histone demethylases suggests a central role for these enzymes in regulating histone methylation dynamics. Histone H3K27 trimethylation (H3K27me3) has been linked to Polycomb Group (PcG) protein-mediated suppression of Hox genes and animal body patterning, X-inactivation and possibly maintenance of embryonic stem (ES) cell identity. An imbalance of H3K27 methylation due to over-expression of the methylase EZH2 has been implicated in metastatic prostate and aggressive breast cancers. Here we show that the related JmjC domain-containing UTX and JMJD3 catalyze demethylation of H3K27me3. UTX is enriched around the transcription start sites of many Hox genes in primary human fibroblasts where Hox genes are differentially expressed, but is selectively excluded from the Hox locus in ES cells in which Hox genes are largely silent. Consistently, RNAi inhibition of UTX led to increased H3K27me3 levels at some Hox gene promoters. Importantly, Morpholino inhibition of a zebrafish UTX homolog resulted in mis-regulation of Hox genes and a striking posterior developmental defect, which was partially rescued by wildtype, but not catalytically inactive human UTX. Taken together, these findings identified a small family of H3K27 demethylases with important, evolutionarily conserved roles in H3K27 methylation regulation and in animal anterior-posterior development.
Keywords: organism_part_comparison_design
Overall design An organism part comparison experiment design type compares tissues, regions, organs within or between organisms.

Controls: UTX occupancy was mapped by chromatin immunoprecipitation using anti-UTX antibody. As control, we performed mock chromatin immunoprecipitation with isotype-matched antibody (IgG). Two color, competitive hybridization experiments were performed to compare genomic DNA enrichment in UTX vs. IgG pulldowns.

Experimental variable: We compared primary human fibroblasts from two different anatomic locations--foot and lung.
Contributor(s) Rinn J, Demeter J
Citation(s) 17851529
Submission date Aug 23, 2007
Last update date Mar 17, 2012
Contact name John Louis Rinn
Phone 650 5752491
Fax 650 5752491
Organization name Stanford University
Department Dermatology
Lab Chang
Street address 2155 CCSR
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL5790 Nimblegen Custom HOX array
Samples (2)
GSM225641 Foot Fibroblast UTX ChIP
GSM225642 Lung Fibroblast UTX ChIP
BioProject PRJNA102209

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE8855_RAW.tar 100.1 Mb (http)(custom) TAR (of GFF, PAIR, TIFF)
Processed data included within Sample table
Processed data provided as supplementary file

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