Chromobox protein homolog 7 (CBX7) (CBX7)

Chromobox protein homolog 7 (CBX7) is a member of the Polycomb group (PcG) proteins and a critical component of the Polycomb Repressive Complex 1 (PRC1) [1.1.1, 1.5.4]. It functions as an epigenetic reader by utilizing its N-terminal chromodomain to recognize and bind trimethylated lysine 27 of histone H3 (H3K27me3), a modification associated with transcriptional silencing [1.1.1, 1.3.1]. This interaction is essential for the recruitment of PRC1 to specific genomic loci, such as the INK4A/ARF tumor suppressor locus, leading to chromatin compaction and gene repression [1.1.2, 1.5.1]. CBX7 is implicated in various biological processes, including stem cell self-renewal, cell cycle regulation, and senescence [1.1.1, 1.5.4]. In disease, CBX7 exhibits a context-dependent role; it acts as an oncogene in prostate and gastric cancers by silencing tumor suppressors, but functions as a tumor suppressor in thyroid and lung cancers where its loss correlates with malignancy [1.2.2, 1.4.3, 1.5.3]. Small molecule antagonists, such as MS37452 and MS351, have been developed to target the CBX7 chromodomain, disrupting its binding to H3K27me3 and promoting the derepression of silenced genes [1.1.1, 1.1.3]. The primary therapeutic challenges include achieving selectivity over other highly homologous CBX family members and navigating the protein's divergent roles across different tissue types [1.1.2, 1.2.2].

Other names

Chromobox homolog 7CBX7Polycomb group protein CBX7

Antagonism of the chromodomain binding to trimethylated lysine 27 of histone H3 (H3K27me3), preventing the recruitment of Polycomb Repressive Complex 1 (PRC1) and leading to the transcriptional derepression of target genes such as p16/CDKN2A.