H2AFZ
H2AFZ: A Key Histone Variant with Intriguing Roles in Gene Regulation and Human Disease
Introduction
H2AFZ is a variant of the histone H2A, one of the five core histones that package DNA in eukaryotes. It is a highly conserved histone that plays a significant role in chromatin structure and gene regulation. This blog post will explore the various aspects of H2AFZ, including its structure, function, associated diseases, and the latest research findings.
Structure and Function
H2AFZ is a dimeric histone composed of two identical H2AFZ subunits. It is characterized by a unique C-terminal extension that distinguishes it from other histone H2A variants. This extension contains a conserved motif known as the Q/E domain.
H2AFZ is incorporated into nucleosomes during DNA replication and repair. It typically occupies the nucleosome entry/exit sites, where it facilitates access of regulatory factors and RNA polymerases to the DNA. H2AFZ also interacts with various chromatin modifiers and remodelers, contributing to the dynamic regulation of chromatin structure and gene expression.
Associated Diseases
Mutations or dysregulation in H2AFZ have been linked to several human diseases, including:
- Myeloid malignancies: Mutations in H2AFZ are commonly found in acute myeloid leukemia (AML) and other myeloid disorders. These mutations lead to abnormal H2AFZ deposition and disruption of normal gene expression.
- Solid tumors: Alterations in H2AFZ have also been reported in various solid tumors, such as lung, breast, and colorectal cancer.
- Neurological disorders: Mutations in H2AFZ have been associated with certain neurological disorders, including autism spectrum disorder (ASD) and schizophrenia.
Did you Know ?
A recent study found that H2AFZ mutations are present in approximately 10% of AML cases. This makes H2AFZ one of the most frequently mutated genes in AML.
