Analysis of gene expression changes by knock-down of hace1 tumour suppressor in zebrafish

Background: In this study we reveal a previously undescribed role of the HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) tumor suppressor protein in normal vertebrate heart development using the zebrafish (Danio rerio) model. We examined the link between the cardiac phenotypes associated with hace1 loss of function to the expression of the Rho small family GTPase, rac1, which is a known target of HACE1 and promotes ROS production via its interaction with NADPH oxidase holoenzymes. We examined expression changes induced by knock-down of hace1 in zebrafish at 48 hpf, the stage when heart abnormalities are observed. This was done by collecting duplicate samples of control and hace1 morphant embryos and performing RNA sequencing on them. Conclusions: Our study demonstrates that HACE1 is critical in the normal development and proper function of the heart via a ROS-dependent mechanism. Overall design: 2 samples of control and hace1 morphant zebrafish embryos at 48 hpf were analyzed

4

Razaghi B, Steele SL, Prykhozhij SV, Stoyek MR, Hill JA, Cooper MD, McDonald L, Lin W, Daugaard M, Crapoulet N, Chacko S, Lewis SM, Scott IC, Sorensen PHB, Berman JN