EZH1 is a protein that plays a role in how genes are regulated within cells. It is involved in fundamental biological processes for proper cellular function and development. Understanding EZH1’s actions helps explain how cells maintain identity and how disruptions can lead to diseases.
What is EZH1
EZH1 (enhancer of zeste homolog 1) is a histone methyltransferase. It adds methyl groups to histones, proteins around which DNA is wound, forming chromatin. These tags influence DNA packing, affecting gene activity. This process is part of epigenetics, which studies changes in gene activity without altering the DNA sequence.
How EZH1 Functions in Cells
EZH1 functions as a catalytic subunit within the Polycomb Repressive Complex 2 (PRC2). This complex modifies histone H3 at lysine 27 (H3K27). EZH1 adds one, two, or three methyl groups to this lysine (H3K27me1, H3K27me2, and H3K27me3). These marks compact chromatin, making DNA less accessible and silencing gene expression. The PRC2/EZH1 complex can also compact chromatin even without the methyltransferase cofactor S-adenosyl-L-methionine (SAM).
EZH1’s Biological Significance
EZH1 contributes to several biological processes, maintaining cellular order. It guides embryonic development, forming tissues and organs. It also contributes to cell differentiation, where less specialized cells become specialized. EZH1 safeguards embryonic stem cell identity and self-renewal. It also maintains existing tissues and cell type identity throughout the body.
EZH1 and Disease States
Dysregulation of EZH1 activity contributes to various diseases, especially cancers. Both increased and decreased EZH1 levels link to tumor growth and spread. Overexpression can suppress apoptosis (programmed cell death), contributing to tumor survival. In lymphomas, excessive EZH1 activity links to abnormal histone methylation and altered gene networks.
Conversely, loss-of-function mutations in EZH1 are observed in neurodevelopmental disorders, highlighting its role in nervous system development. EZH1 is also implicated in oral squamous cell carcinoma, competing with EZH2 to promote cancer progression. Its role extends to maintaining tissue integrity during environmental changes, suggesting involvement in cellular stress responses that, when disrupted, contribute to disease.
EZH1 vs EZH2 Unique Roles
EZH1 is a paralog of EZH2, related proteins with similar functions. Both EZH1 and EZH2 serve as catalytic subunits of PRC2 and mediate H3K27 methylation. However, they have distinct expression patterns and histone methyltransferase activity levels. EZH1 often functions as a compensatory mechanism, becoming more active when EZH2 is absent or inhibited.
EZH1 also has specific functions in tissues or developmental stages where EZH2 is less active. For example, EZH1 is the most upregulated histone methyltransferase during dendritic cell maturation, suggesting a unique role in immune responses. While both proteins compact chromatin, studies suggest PRC2/EZH1 may do so more efficiently than PRC2/EZH2, creating a denser chromatin environment that aids H3K27 methylation.