ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development

• DOI: 10.1242/dev.202617
• Publication Date: 2024-08-14T13:32:09Z
• Authors: Sophia Y. Y. Mah; Hannah K. Vanyai; Connie S. N. Li-W...; Alexandra L. Garnham; Jessica Wynn; Maria I. Bergamasco; Shezlie Malelang; Stephen Wilcox; Christine Biben; Gordon K. Smyth; Tim Thomas; Anne K. Voss
• Keywords: Lineage (genetic); Histone H4

ABSTRACT Inhibitor of growth 4 and 5 (ING4, ING5) are structurally similar chromatin-binding proteins in the KAT6A, KAT6B KAT7 histone acetyltransferase protein complexes. Heterozygous mutations KAT6A or gene cause human disorders with cardiac defects, but contribution their chromatin-adaptor to development is unknown. We found that Ing5−/− mice had isolated ventricular septal defects. Ing4−/−Ing5−/− embryos failed undergo chorioallantoic fusion arrested at embryonic day 8.5, displaying loss H3 lysine 14 acetylation, reduction 23 acetylation levels reduced developmental expression. Embryonic 12.5 Ing4+/−Ing5−/− hearts showed a paucity epicardial cells epicardium-derived cells, failure myocardium compaction, coronary vasculature accompanied by expression epicardium genes. Cell adhesion proepicardium outgrowth were defective ING4- ING5-deficient state. Our findings suggest ING4 ING5 essential for heart promote cell fates imply mutation as possible