Table 1 Summary of epigenetic modulating proteins with known roles in mammary gland development
Protein complex or family | Members | Modification | Activating/repressive | Role in MG development | Reference | |
|---|---|---|---|---|---|---|
DNA methyltransferase | DNMT1, DNMT3a, DNMT3b | DNA methylation | Repressive at promoters, activating in gene bodies | DNMT1 maintains stem/progenitor cells | [33] | |
Polycomb repressive complex 2 (PRC2) | SUZ2, EED, RBBP4 or RBBP7 and EZH2 or EZH1 | H3K27 trimethylation | Repressive | EZH2 maintains stem/progenitor cells, restricts mature luminal differentiation, and promotes alveolar differentiation. | ||
Polycomb repressive complex 1 (PRC1) | PCGF | BMI1 or MEL18 | H2AK119 mono-ubiquitylation | Repressive | BMI1 maintains stem/progenitor cells and restricts alveolar differentiation | [52] |
CBX | CBX2, CBX4, CBX6, CBX7, or CBX8 | |||||
PHC | PHC1, PHC2, or PHC3 | |||||
SCML | SCMH1 or SCML2 | |||||
RING | RING2 or RING1 | |||||
Lysine demethylase (KDM) proteins | JARID1B/KDM5B/PLU-1 | H3K4Me3 demethylation | Repressive and activating | GATA3 cofactor, promotes luminal differentiation | ||
JMJD2B/KDM4B | H3K9Me3 demethylation | Activating | ERα cofactor, promotes luminal differentiation | [61] | ||
KDM6A/UTX | H3K27Me3 demethylation | Activating | Luminal transcription factor co-factor, promotes luminal differentiation | [62] | ||
Plant homeodomain (PHD)-containing proteins | Pygo2 | Binds to H3K4Me3 | Not applicable | β-catenin co-factor, maintains stem/progenitor cells by restricting Notch-mediated luminal differentiation | [65] | |
Bromodomain and extra-terminal domain (BET) proteins | BRD4 | Binds to acetylated lysines on histones | Activating | FOXO1 cofactor, maintains basal epithelial phenotype | [76] | |