GSE111691
TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for developmental gene regulation and organogenesis
Multiple varieties of most chromatin regulatory complexes are expressed in mammals, resulting from a combination of alternative splicing, differential incorporation of accessory subunits, and other processes. Despite this complexity, chromatin regulators are usually characterized in vivo using mutants that affect multiple forms. Here we examine the developmental functions of the TIP55 isoform of the KAT5 (TIP60) histone acetyltransferase. In contrast to the preimplantation developmental arrest of mice deficient for all four Kat5 transcripts, mice specifically deficient for Tip55 die around E11.5 and fail to develop beating hearts . Prior to developmental arrest, mice exhibit altered proliferation and cell death in heart and neural tube, respectively. Consistent with these findings, transcriptome profiling prior to the onset of overt morphological abnormalities reveals alterations in multiple tissue types. These findings reveal that although Tip55 is dispensable for the pre- and early post-implantation roles of Kat5, it is essential for organogenesis. Targeted mutations of additional Kat5 isoforms will be necessary to understand their specific functions. Furthermore, targeted mutations of individual isoforms of other chromatin remodeling enzymes will likely uncover new biological functions. Overall design: The data represent RNA-seq experiments examining gene expression changes in Tip55 knockout embryos relative to controls.