Table 3.

Histone modification factors associated with EMT of TNBC.

Histones Modifications Factors	Targets and Pathways	Sense of Dyregulation in TNBC	Role of histone modifications in TNBC	References
TIP60 Lysine acetyltransferase	Destabilize DNMT1 and inhibit SNAIL2 function leading to the inhibition of DNA methylation of EpCAM promoter region activating the expression of epithelial markers.	Downregulated	Anti-tumoural	[103]
KDM6A H3K27me3-demethylase	Maintenance of CDH1/E-cadherin levels. Role in the MET-associated resolution. Reactivation of bivalent genes by removing H3K27me3 marks deposited during EMT.	Downregulated	Anti-tumoural	[104]
EZH2 Histone-lysine N-methyltransferase (H3K27me3)	Induce the repression of TIMP2 transcription increasing MMP-2 and MMP-9 activity.	Up-regulated	Pro-tumoural	[105]
LSD1 Lysine demethylase 1	Represses E-cadherin expression by demethylating H3K4me at gene’s promoter, during which phosphorylation of LSD1 Ser112 is crucial.	Up-regulated	Pro-tumoural	[106]
hSETD1A H3K4 Methyltransferase	Activates MMPs expression (MMP2, MMP9, MMP12, MMP13, and MMP17).	Up-regulated	Pro-tumoural	[107]
JMJD5 H3K36me2 demethylase	Promote cell invasion and induce EMT. Catalyze Snail promoter H3K36me2 demethylation activating its expression.	Up-regulated	Pro-tumoural	[108]
KDM5B Lysine-specific demethylase 5B	Overexpress MALAT1. Overexpress EMT markers, c-Met, Slug and N-Cadherin, and inhibitis E-Cadherin.	Up-regulated	Pro-tumoural	[109]
KDM3A H3 lysine 9 demethylase 3A	Promotes the expression of invasive genes by erasing H3K9me2 marks. Regulates the expression of MMP-9 and JUN expressions.	not evaluated	Pro-tumoural	[110]
HDAC8 Zinc-dependent class I HDAC	Enhance TNBC cell migration. Regulates YAP protein levels by decreasing YAP phosphorylation at Ser127.	not evaluated	Pro-tumoural	[111]