Table 1.

Epigenetic layers and players and their human disease associations

	Full name and function	Human neuronal disease association	Refs
Layers	Modifications of DNA or chromatin
5hmeC	5-hydroxymethylcytosine		[13]
5mC	5-methylcytosine		[14, 15]
PMD	Partially methylated domain		[12]
HMD	Highly methylated domain		[3]
N-HMD	Neuronal highly methylated		[3, 24]
ICR	Imprinting control region	Prader-Willi, Angelman	[20, 21]
PcG	Polycomb group gene		[36] [24]
H3K27me3	Histone H3 trimethylation at lysine 27		[36]
H3K4me3	Histone H3 trimethylation at lysine 4		[36]
H3K36me3	Histone H3 trimethylation at lysine 36		[36]
H3K27ac	Histone H3 acetylation at lysine 27		[36]
H3K9ac	Histone H3 acetylation at lysine 9		[36]
CGI	CpG island, nonrandom cluster of CpG sites, association with gene promoters		[92]
R-loop	RNA/DNA hybrid formed at transcribed regions with high G skew, protects active promoter CGIs from DNA methylation		[92]
eRNA	Enhancer RNA, noncoding RNAs transcribed from active enhancers, implicated in long- range looping interactions		[68]
antisense RNA	Noncoding RNA transcribed in the opposite strand orientation from a protein coding gene, inhibition of transcriptional elongation of sense transcript		[70] [91]
Players	Enzymes or protein complexes that direct epigenetic layers
DNMT1	DNA methyltransferase 1, maintenance DNA methylation		[25] [27]
DNMT3A	DNA methyltransferase 3A, de novo DNA methylation		[26] [28]
DNMT3B	DNA methyltransferase 3B, de novo DNA methylation	immunodeficiency, centromeric instability, facial dysmorphism (ICF)	[109]
PRC1, PRC2	Polycomb repressive complex 1 and 2, regulation of polycomb group genes		[64, 79]
EZH2	Enhancer of Zeste, Drosophila homologue 2, methyltransferase for H3K27		[64, 79]
MeCP2	Methyl CpG binding protein 2, abundant nuclear factor in mature neurons, activity- dependent transcriptional responses	Rett syndrome, MECP2 duplication syndrome	[56] [110]
ATRX	Nuclear factor with Zinc finger, ATPase, and helicase domains, similarities to SNF2H chromatin remodeling protein	Alpha-thalassemia/Mental retardation, X linked	[111]
BAF53b	Actin-like component of neuronal chromatin remodeling complex, implicated in synaptic plasticity		[41] [42]
ARID1B	Component of neuronal BAF chromatin remodeling complex	Coffin-Siris syndrome	[40, 112]
JMJD1C/TRP8	Histone demethylase for H3K9, hormone-dependent transcriptional activation	X-linked intellectual disability, autism	45 [113]
KDM5C/JARD1C	Histone demethylase of H3K4, gene repression	X-linked intellectual disability, autism	[47, 114]
SMCA1/cohesin	Cohesion, structural maintenance of chromosomes 1A, chromatin looping	Cornelia de Lange	[115]
Mediator	Multiprotein complex and general regulator of transcription, transcriptional coactivator, chromatin looping, activating-RNA binding		[91]
CTCF	CCCTC-binding factor, chromatin insulator, chromatin looping		[51] [50]
CREBBP (CBP)	CREB binding protein, H3K56 acetyltransferase, activity- dependent transcriptional responses	Rubinstein-Taybi syndrome	[116] [117]
TET1	TET oncogene, family member 1, methylcytosine dioxygenase, converts 5mC to 5hmC resulting in demethylation		[14, 15]
MLL1	Mixed lineage leukemia 1, H3K4 methyltransferase	Wiedemann-Steiner syndrome	[118]
lncRNA	Long, non-coding RNA, >200nt with low-protein coding potential		[72] [73]
Xist	X chromosome inactivation specific transcript		[60]