E3 ubiquitin-protein ligase BRE1A

RNF20 (also known as BRE1A) is an E3 ubiquitin-protein ligase that forms a functional complex with RNF40 to mediate monoubiquitination of histone H2B at lysine 120 (H2BK120ub1) (UniProt: Q5VTR2). This histone modification is a critical epigenetic mark for transcriptional activation and serves as a prerequisite for downstream H3K4 and H3K79 methylation, thereby regulating the histone code and gene expression. RNF20 is also involved in transcriptional coactivation at specific promoters including MDM2 and has documented roles in herpesvirus infection pathways.

RNF20 is expressed broadly across tissues and functions primarily in chromatin remodeling and gene regulation through its role in the histone ubiquitination machinery (UniProt: Q5VTR2). The protein operates as part of a larger epigenetic regulatory network affecting multiple biological processes from development to viral response.

In Alzheimer's disease, RNF20 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.28 across subcellular fractions (Chaparral AD proteomics). This elevation suggests potential dysregulation of histone-mediated chromatin remodeling and gene expression in AD pathology, though the functional consequences of this upregulation remain to be determined.