HAT1: Landscape of Biological Function and Role in Cancer

Abstract

Histone modifications, as key chromatin regulators, play a pivotal role in the pathogenesis of several diseases, such as cancer. Acetylation, and more specifically lysine acetylation, is a reversible epigenetic process with a fundamental role in cell life, able to target histone and non-histone proteins. This epigenetic modification regulates transcriptional processes and protein activity, stability, and localization. Several studies highlight a specific role for HAT1 in regulating molecular pathways, which are altered in several pathologies, among which is cancer. HAT1 is the first histone acetyltransferase discovered; however, to date, its biological characterization is still unclear. In this review, we summarize and update the current knowledge about the biological function of this acetyltransferase, highlighting recent advances of HAT1 in the pathogenesis of cancer.

Keywords: HAT1; acetylation; cancer; epigenetics; inflammation.

Figure 1

Graphical illustration of HAT1 function. Interaction of the Hat1/Rbap46 complex with histones in the cytoplasm and subsequent transfer into the nucleus via importin, binding histone chaperone protein. Once inside the nucleus, HAT1 interacts with CAF1 and facilitates the pathway for deposition of newly synthesized histones to regulate gene transcription.

Figure 2

Schematic diagram of the structure of HAT1 protein.

Figure 3

Representative enzymatic function of HAT1.

Figure 4

Overview of HAT1 expression in human cancer. (A) Schematic representation of the different expression levels of HAT1 in the described cancer. The red and green squares represent the upregulation or downregulation of HAT1 expression levels, respectively. (B) The box plot depicts RNA expression levels in 17 different types of cancer from the TCGA dataset; ♦ represent outliers that differ significantly from the rest of the dataset.