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

Mah, SYY; Vanyai, HK; Li-Wai-Suen, CSN; Garnham, AL; Wynn, J; Bergamasco, MI; Malelang, S; Wilcox, S; Biben, C; Smyth, GK; Thomas, T; Voss, AK

Author(s): Mah, SYY; Vanyai, HK; Li-Wai-Suen, CSN; Garnham, AL; Wynn, J; Bergamasco, MI; Malelang, S; Wilcox, S; Biben, C; Smyth, GK; Thomas, T; Voss, AK;
Details: Publication Year 2024-03-01,Volume 151,Issue #5,Page dev202617
Journal Title: Development
Abstract: Inhibitor of growth 4 and 5 (ING4, ING5) are structurally similar chromatin-binding proteins in the KAT6A, KAT6B and KAT7 histone acetyltransferase protein complexes. Heterozygous mutations in the KAT6A or KAT6B gene cause human disorders with cardiac defects, but the contribution of their chromatin-adaptor proteins to development is unknown. We found that Ing5-/- mice had isolated cardiac ventricular septal defects. Ing4-/-Ing5-/- embryos failed to undergo chorioallantoic fusion and arrested in development at embryonic day 8.5, displaying loss of histone H3 lysine 14 acetylation, reduction in H3 lysine 23 acetylation levels and reduced developmental gene expression. Embryonic day 12.5 Ing4+/-Ing5-/- hearts showed a paucity of epicardial cells and epicardium-derived cells, failure of myocardium compaction, and coronary vasculature defects, accompanied by reduced expression of epicardium genes. Cell adhesion gene expression and proepicardium outgrowth were defective in the ING4- and ING5-deficient state. Our findings suggest that ING4 and ING5 are essential for heart development and promote epicardium and epicardium-derived cell fates and imply mutation of the human ING5 gene as a possible cause of isolated ventricular septal defects.
Keywords: Humans; Animals; Mice; Cell Lineage; *Lysine; Histones; Acetylation; *Heart Septal Defects, Ventricular; Chromatin; Transcription Factors; Tumor Suppressor Proteins; Homeodomain Proteins/genetics; Cell Cycle Proteins; Histone Acetyltransferases; *Carrier Proteins; H3k14; Heart development; Histone acetylation; Ing4; Ing5; Inhibitor of growth proteins
Research Division(s): Advanced Technology And Biology; Bioinformatics; Epigenetics And Development; Bioinformatics; Advanced Technology and Biology
PubMed ID: 38446206
Publisher's Version: https://doi.org/10.1242/dev.202617
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-11 09:24:53

Last Modified: 2024-03-11 09:33:54