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Series GSE85505 Query DataSets for GSE85505
Status Public on Apr 06, 2017
Title KAT–independent gene regulation by Tip60 promotes ESC self-renewal but not pluripotency
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Although histone-modifying enzymes are assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here we show the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT–deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT–independent role of Tip60 in ESC maintenance. In contrast, KAT–deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a second, KAT–dependent function in differentiation. Consistent with this phenotype, KAT–deficient mouse embryos exhibited post-implantation developmental defects. These findings establish separable KAT–dependent and KAT–independent functions of Tip60 in ESCs and during embryonic development, raising the possibility of undiscovered catalysis-independent functions of additional KATs.
Overall design The data represent several experiments: (1) RNA-seq experiments examining gene expression changes in Tip60 catalytic inactive, Ep400 catalytic inactive, double mutants, or knockdowns (RNAi) in ESCs relative to controls, (2) RNA-seq experiments examining changes in gene expression of wild type controls and Tip60 catalytic inactive mutants during ESC differentiation, and (3) ATAC-seq experiments examining chromatin accessibility in control, Tip60 catalytic inactive, and Tip60 knockdown ESCs.
The data represent ChIPseq experiment examining changes in H4 acetylation and H2AZ occupany in Tip60 catalytic inactive and Ep400 catalytic inactive mutant ESCs respectively, relative to controls.
Contributor(s) Acharya D, Hainer SJ, Yoon Y, Wang F, Bach I, Rivera-Pérez JA, Fazzio TG
Citation(s) 28445719
Submission date Aug 11, 2016
Last update date May 15, 2019
Contact name Thomas Fazzio
Organization name UMMS
Street address 364 Plantation street
City Worcester
State/province MA
ZIP/Postal code 01605
Country USA
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (48)
GSM2267932 EGFPKD_RNAseq_Rep1
GSM2267933 EGFPKD_RNAseq_Rep2
GSM2267934 Tip60KD_RNAseq_Rep1
BioProject PRJNA338692
SRA SRP081300

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Supplementary file Size Download File type/resource
GSE85505_RAW.tar 6.7 Gb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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