AI Article Synopsis
- ING4 and ING5 are proteins that help regulate gene expression and are part of histone acetyltransferase complexes involved in heart development.
- Mutations in genes like KAT6A and KAT6B are linked to heart defects, and studies on mice with disrupted ING4 and ING5 reveal serious developmental issues, including heart defects.
- The absence of these proteins leads to problems with cell development, structure, and gene expression during early embryonic stages, suggesting mutations in ING5 may contribute to human heart conditions like ventricular septal defects.*
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1242/dev.202617 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.
Cell Mol Biol Lett
November 2024
Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation.
View Article and Find Full Text PDFING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development.
Development
March 2024
Walter and Eliza Hall Institute of Medical Research, Epigenetics and Development Division, Melbourne, VIC 3052, Australia.
Article Synopsis
- ING4 and ING5 are proteins that help regulate gene expression and are part of histone acetyltransferase complexes involved in heart development.
- Mutations in genes like KAT6A and KAT6B are linked to heart defects, and studies on mice with disrupted ING4 and ING5 reveal serious developmental issues, including heart defects.
- The absence of these proteins leads to problems with cell development, structure, and gene expression during early embryonic stages, suggesting mutations in ING5 may contribute to human heart conditions like ventricular septal defects.*
Newly identified tumor suppressor functions of ING proteins.
Curr Opin Pharmacol
February 2023
Univ Rennes 1, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, F-35000, Rennes, France. Electronic address:
The INhibitor of Growth (ING) proteins (ING1, ING2, ING3, ING4 and ING5) are a family of epigenetic regulators. Their decreased expression in numerous cancers led to identifying the ING proteins as gatekeeper tumor suppressors as they regulate cell cycle progression, apoptosis and senescence. Subsequently, they were also described as caretaker tumor suppressors through their involvement in DNA replication and the DNA damage response (DDR).
View Article and Find Full Text PDFThe roles of ING5 in cancer: A tumor suppressor.
Front Cell Dev Biol
November 2022
Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
As a Class II tumor suppressor, ING5 contains nuclear localization signal, plant homeodomain, novel conserved region, and leucine zipper-like domains. ING5 proteins form homodimer into a coil-coil structure, and heterodimers with ING4, histone H3K4me3, histone acetyltransferase (HAT) complex, Tip60, Cyclin A1/CDK2, INCA1 and EBNA3C for the transcription of target genes. The acetylated proteins up-regulated by ING5 are preferentially located in nucleus and act as transcription cofactors, chromatin and DNA binding functions, while those down-regulated by ING5 mostly in cytoplasm and contribute to metabolism.
View Article and Find Full Text PDFAn study of how histone tail conformation affects the binding affinity of ING family proteins.
PeerJ
January 2023
Faculty of Engineering, Turkish-German University, Istanbul, Turkey.
Background: Due to its intrinsically disordered nature, the histone tail is conformationally heterogenic. Therefore, it provides specific binding sites for different binding proteins or factors through reversible post-translational modifications (PTMs). For instance, experimental studies stated that the ING family binds with the histone tail that has methylation on the lysine in position 4.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!