Histone deacetylase 1 and 2 regulate Wnt and XXXX pathways in the ureteric bud epithelium.

@entity8 @entity12231 @entity19 @entity5 @entity899 @entity30653
Histone deacetylases (HDACs) regulate a broad range of biological processes through removal of acetyl groups from histones as well as non-histone proteins. Our previous studies showed that @entity12231 and @entity30653 are bound to promoters of key renal developmental regulators and that HDAC activity is required for embryonic kidney gene expression. However, the existence of many HDAC isoforms in embryonic kidneys raises questions concerning the possible specificity or redundancy of their functions. We report here that targeted deletion of both the @entity12231 and @entity30653 genes from the ureteric bud (UB) cell lineage of @entity19 causes bilateral @entity8 . One copy of either @entity12231 or @entity30653 is sufficient to sustain normal renal development. In addition to defective cell proliferation and survival, genome-wide transcriptional profiling revealed that the canonical Wnt signaling pathway is specifically impaired in UB( @entity12231 ,2-/-) kidneys. Our results also demonstrate that loss of @entity12231 and @entity30653 in the UB epithelium leads to marked hyperacetylation of the @entity5 suppressor protein @entity899 on lysine 370, 379 and 383; these post-translational modifications are known to boost @entity899 stability and transcriptional activity. Genetic deletion of @entity899 partially rescues the development of UB( @entity12231 ,2-/-) kidneys. Together, these data indicate that @entity12231 and @entity30653 are crucial for kidney development. They perform redundant, yet essential, cell lineage-autonomous functions via @entity899 -dependent and -independent pathways.
