Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy

Table 1

The summary of DNA methylation, histone methylation, and histone acetylation changes in multiple cell types and animal models of FRDA.

Chromatin change	Location	Patients/cell type/animal model	Reference(s)
DNA methylation ↑	GAA upstream	Lymphoblasts, FRDA YAC transgenic mice, and primary lymphocytes	[36, 38–40]
H3K4me2/3 ↓	FXN promoter and exon 1	Lymphoblasts	[61, 68, 69]
	GAA upstream	Lymphoblasts	[68, 69]
	GAA downstream	Lymphoblasts	[68, 69]
H3K9me2/3 ↑	FXN 5′-UTR/promoter	Primary fibroblasts and lymphoblasts	[63, 68]
	GAA upstream	Lymphoblasts, FRDA YAC transgenic mice, and KIKI mice	[38, 60–62, 68, 69]
	GAA downstream	FRDA patients, FRDA YAC transgenic mice, and lymphoblasts	[38, 60, 61, 68, 69]
H3K27me3 ↑	FXN 5′-UTR/promoter	Primary fibroblasts and lymphoblasts	[63, 68]
	GAA upstream	Lymphoblasts	[68]
	GAA downstream	Lymphoblasts	[68]
H3K36me3 ↓	GAA upstream	Lymphoblasts	[61, 68, 69]
	GAA downstream	Lymphoblasts	[61, 68, 69]
H3K79me2 ↓	GAA upstream	Lymphoblasts	[68]
	GAA downstream	Lymphoblasts	[68]
H4K20me3 ↑	GAA upstream	Lymphoblasts	[68]
	GAA downstream	Lymphoblasts	[68]
H4K5ac ↓	FXN promoter	Lymphoblasts	[69]
	GAA upstream	Lymphoblasts and KIKI mice	[60, 62, 69]
	GAA downstream	FRDA patients, FRDA YAC transgenic mice, and lymphocytes	[38, 62, 69]
H3K9ac ↓	FXN promoter	FRDA patient brain tissue and lymphoblasts	[38, 69]
	GAA upstream	FRDA patients, FRDA YAC transgenic mice, lymphoblasts cells, and KIKI mice	[38, 60, 69]
	GAA downstream	FRDA patients, FRDA YAC transgenic mice, and lymphoblasts	[38, 60, 69]
H4K8ac ↓	GAA upstream	Lymphoblasts, FRDA patients, and KIKI mice	[38, 60, 62, 69]
	GAA downstream	Lymphoblasts and FRDA patients	[60, 69]
H4K12ac ↓	FXN promoter	Lymphoblasts	[60]
	GAA upstream	Lymphoblasts, FRDA patients, and FRDA YAC transgenic mice	[38, 60]
	GAA downstream	Lymphoblasts, FRDA patients, and FRDA YAC transgenic mice	[38, 60]
H3K14ac ↓	FXN promoter	FRDA patients	[38]
	GAA upstream	KIKI mice and lymphoblasts	[62, 69]
	GAA downstream	FRDA YAC transgenic mice and lymphoblasts	[69]
H4K16ac ↓	FXN promoter	Lymphoblasts	[62, 69]
	GAA upstream	Lymphoblasts, FRDA patients, FRDA YAC transgenic mice, and KIKI mice	[38, 60, 62, 69]
	GAA downstream	Lymphoblasts, FRDA patients, FRDA YAC transgenic mice, and KIKI mice	[38, 60, 62, 69]

↓: reduced, ↑: increased, H: histone, K: lysine, me2: dimethylation, me3: trimethylation, ac: acetylation, and HP: heterochromatin protein.