Tissue-specific localization of the ING4 targeting subunit of the HBO1 histone acetyltransferase in the cytoplasm and nucleus of secretory cells.

Abstract

Members of the INhibitor of Growth protein family (ING1-5) function as epigenetic regulators by targeting different histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes to the H3K4Me3 mark of active transcription. The INGs recognize H3K4Me3 by specific interaction with their well-conserved plant homeodomains, and affinity can be increased by interactions between DNA and disordered regions within the ING proteins. They are classified as type II tumor suppressors since they are downregulated in numerous cancer types and knockout of ING family members results in tumorigenesis. ING4 targets the HBO1 HAT complex, which is known to affect acetylation of the H4 core nucleosomal histone, to affect local chromatin structure and knockout results in deficient innate immunity. Reports indicating roles in cell cycle regulation, tumor suppression, and apoptosis suggest that ING4 may be a promising target for cancer treatment by targeting pathways of innate immunity. Given the relatedness between ING4 and the closely related ING5 proteins, we have developed and characterized two mouse monoclonal antibodies to specifically recognize human and mouse ING4, but not ING5, to more accurately characterize ING4 levels by western, immunofluorescence and immunohistochemical assays. Using them, we show that ING4 differentially partitions between the nucleus and cytoplasm in different tissues and localizes largely to the cytoplasm of cells having a secretory role in different tissue types.