T2DM: Why Epigenetics?

Table 1

A glimpse at the epigenetic agenda in the T2DM context.

		Genome	Epigenome	Immediate environment	Known relations; with T2D
Germ cells	Oocyte	Meiosis I completed Meiosis II arrested	Establishment of methylation imprints		Maternal diabetes increases oocyte apoptosis
	Spermatozoan		Establishment of methylation imprints; Displacement of histones by protamines
Fecundation
One-cell zygote to morula	Female DNA	Meiosis II completed	Passive DNA demethylation
			Imprinted genes retain their germline imprints.
	Male DNA		Protamines/histones exchange Histone acetylation	Oviductal (maternal)	“Fertility ?”
			Histone monomethylation
			Active DNA demethylation
			Methylation remains in centromeric regions, IAP retrotransposons, and paternal imprinted regions
	Both sex		Histone di- and trimethylation
Implantation
Foetus	Embryo XX	PGC female: meiosis I	X inactivation; PGC: DNA demethylation and imprint erasure	Placental (maternal)	Maternal T2DM/GDM increases embryo malformations.
	Embryo XY		PGC: DNA demethylation and imprint erasure and then DNA remethylation in prospermatogonia		Maternal nutrition changes DNA methylation on key metabolic genes: PPARα, IGF2, …, etc.
	Both sexes		De novo DNA methylation Ectoderm (brain), endoderm (liver, β cells), mesoderm (skeletal muscle, adipose tissue, blood); Tissue differentiation: T-DMRs
Birth
Baby/child	Girl; Boy; Both sexes		PGC: DNA remethylation; —; Stochastic modifications	Whole organism	Delivery of a macrosomic fetus.; Nutrition affects DNA methylation of key metabolic genes: FASN, POMC, …, etc.; Insulin and glucose effects on methionine metabolism
Puberty
Adulthood
	Both sexes		Aging: stochastic modifications	Whole organism