Ubiquitin ligases, often referred to as E3 ligases, are a class of enzyme usually involved in the regulation of protein stability and degradation. Whilst they are traditionally associated with protein turnover, they play additional roles in epigenetic processes. Ubiquitin ligases can monoubiquitinate histone proteins, particularly histone H2A and H2B, leading to alterations in chromatin structure. This modification can either activate or repress gene expression, depending on the specific residue and context. For example, mono-ubiquitylation of histone H2B (H2Bub1) is often associated with active transcription, whilst ubiquitination of histone H2A at lysine 119 (H2Aub1) is linked to gene repression. Histone ubiquitination by ubiquitin ligases contributes to epigenetic memory, whereby specific chromatin states are maintained across cell divisions. For instance, the Polycomb Repressive Complex 1 (PRC1) catalyses the ubiquitylation of H2A at lysine 119 (H2Aub1), stabilizing repressive chromatin states and gene silencing. Ubiquitin ligases can also target transcription factors for degradation or modulate their activity through ubiquitylation. For example, the ubiquitin ligase MDM2 targets the tumour suppressor p53 for ubiquitylation and subsequent degradation, thus regulating p53-mediated transcriptional responses. Ubiquitylation of other transcription factors also influences gene expression patterns and epigenetic states. For instance, the transcription factor c-Myc is regulated by ubiquitin ligases, and its degradation by the ubiquitin-proteasome system is essential for maintaining proper gene expression profiles. Two prominent ubiquitin ligases that regulate c-Myc are FBXW7 (also known as CDC4) and SKP2 (S-phase kinase-associated protein 2). FBXW7 is an F-box protein and part of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. FBXW7 targets c-Myc for ubiquitylation by recognizing specific phosphor-degron motifs in c-Myc, which are phosphorylated by kinases such as GSK3β and CK1. Ubiquitin ligases also play an important role in DNA repair processes. For example, the RNF8 and RNF168 ubiquitin ligases are involved in the ubiquitination of histone H2A and H2AX at sites of DNA damage, facilitating the recruitment of DNA repair factors to damaged sites. This ubiquitin signalling is therefore essential for genome stability. DNA damage and repair can lead to changes in epigenetic marks at sites of damage. Ubiquitin ligases participate in these processes by modifying histones and chromatin structure to promote efficient DNA repair. Dysregulation of ubiquitin ligases is implicated in various cancers. For example, the E3 ubiquitin ligase UHRF1 is involved in the maintenance of DNA methylation patterns, and its overexpression can lead to aberrant DNA methylation and gene silencing in cancer. Mutations in ubiquitin ligases are also linked to neurodevelopmental disorders such as Angelman syndrome, where the E3 ubiquitin ligase UBE3A is disrupted. UBE3A is involved in the ubiquitylation and degradation of specific target proteins in neurons. Thus, ubiquitin ligases play multifaceted roles in epigenetics by regulating histone modifications, transcription factors, and DNA repair processes. Their activities are crucial for maintaining proper gene expression patterns, epigenetic memory, and genome stability. We offer a comprehensive product range of research reagents for studying ubiquitin ligases, including MURF1 antibodies, NEDD4 antibodies, and EDD antibodies. Explore our full ubiquitin ligase product range below and discover more, for less.