Celiac disease: From genetics to epigenetics

Table 2 Celiac disease-relevant histone modifications

Modification		Focus	Result	Relevance in CeD
H3K27ac[36]	Activation and enhancing of transcription	Profiling in stimulated CTLs from CeD subjects	IL-15, IFNβ and IL-21 induce specific acetylation profiles in CTLs	Strong association between H3K27ac and gene expression IFNβ-induced
				IL-15-derived changes related to lncRNAs
H3K4me3[37]	Active transcription marker	Shared variants between CeD and RA	Similar histone enrichment in shared variants in simple cells	Different histone enrichment in disease-related specialized cells
H3K36me3[38]	Active transcription marker	SETD2 silenced in 32% of EATL	↓H3K36me3 → γδT cells expansion	Predisposition to lymphomagenesis
H3K27me3[39]	Gene silencing	PRC2–driven trimethylation	Villi → H3K27me3 on proliferation and differentiation genes	PRC2 methylation help maintenance of Wnt homeostasis → deregulation linked to CeD crypts hyperplasia
			Crypts → H3K27me3 on nutrient transport and cell killing genes

CeD: Celiac disease; CTLs: Cytotoxic T lymphocytes; LncRNAs: Long non-coding RNAs; ECM: Extracellular matrix; RA: Rheumatoid arthritis; EATL: Enteropathy associated T cell lymphoma; PRC2: Polycomb repressive complex 2.