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Series GSE41710 Query DataSets for GSE41710
Status Public on Oct 19, 2012
Title Global gene expression analysis of Dot1l-deficient and control intestinal villus cells in mouse
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Methylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes. Recent studies suggest that Wnt-responsive genes depend particularly on H3K79 methylation, which is catalyzed by the methyltransferase DOT1L. Human leukemias carrying MLL gene rearrangements show DOT1L-mediated H3K79 methylation and aberrant expression of leukemogenic genes. DOT1L inhibitors reverse these effects but their clinical use is potentially limited by toxicity in Wnt-dependent tissues such as intestinal epithelium. Genome-wide positioning of the H3K79me2 mark in Lgr5+ mouse intestinal stem cells and mature intestinal villus epithelium correlated with mRNA expression levels but not with Wnt-responsive genes per se. Selective Dot1l disruption in Lgr5+ stem cells or in all intestinal epithelial cells eliminated H3K79me2 from the respective compartments, allowing genetic evaluation of DOT1L requirements. Absence of methylated H3K79 did not impair health, intestinal homeostasis or expression of Wnt target genes in crypt epithelium for up to 4 months, despite increased crypt cell apoptosis. Global transcript profiles in Dot1l-null cells were barely altered. Thus, H3K79 methylation is not essential for transcription of Wnt-responsive or other intestinal genes and intestinal toxicity is not imperative when DOT1L is rendered inactive in vivo.
Overall design Examination of differential gene expression between Dot1l control (Dot1 f/f) and Dot1l mutant (Villin-Cre, Dot1l f/f) villus cells.
Contributor(s) Ho LL, Sinha AU, Armstrong SA, Shivdasani R
Citation(s) 23428873
Submission date Oct 19, 2012
Last update date May 15, 2019
Contact name Amit Sinha
Phone 617-582-7579
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Lab Armstrong Lab
Street address 44 Binney St
City Boston
State/province MA
ZIP/Postal code 02135
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM1023015 Dot1l_wildtype
GSM1023016 Dot1l_mutant
This SubSeries is part of SuperSeries:
GSE41543 DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions
BioProject PRJNA178007
SRA SRP016565

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Supplementary file Size Download File type/resource
GSE41710_RAW.tar 1.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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