Table 1.

Summary of epigenetic mechanisms and their role in memory cell development

Mechanism	Cell type/species	Role	Ref
PTMs
Acetylation	Memory CD4+/CD8+ T cells	▪ Marks memory responsive genes for rapid reactivation	[15]
		▪ Form stable marks of transcriptional activation that are retained in memory T cells	[11-14]
Methylation	Memory CD4+/CD8+ T cells	▪ Loss of repressive histone methylation marks at active genes are preserved in memory T cells to facilitate faster transcription of target genes	[16,17]
Histone variants
H3.3	mES cells	▪ Marks gene enhancers for rapid reactivation	[37,38]
		▪ Primes genes for transcription by destabilising nucleosome structure to facilitate recruitment of transcription factors
	Xenopus	▪ Required for transcriptional memory following somatic cell transfer	[47]
	pre-B cells	▪ Forms stable marks of transcriptional activity that persist through cell division	[49]
H2A.Z	Yeast/CD4+ T cells	▪ Destabilises chromatin structure to facilitate recruitment of transcription machinery	[29-31]
	Yeast	▪ Regulates the localisation of recently repressed genes to the nuclear periphery to facilitate transcriptional memory	[48]
H2A.Lap1	Mouse testis cells	▪ Selectively recruited at the TSS of active genes to destabilise nucleosomal structure and facilitate transcriptional reactivation	[51,52]
Transcription factors
STAT3	Memory CD8+ T cells	▪ Regulates the expression of pro-memory transcription factors essential for generation of memory T cells	[65,68]
Tcf1	Memory CD8+ T cells	▪ Regulates memory T cell formation and immune responses through the induction of Eomesodermines and regulation of pro-memory transcription factors	[67,68]
FOXO1	Memory CD8+ T cells	▪ Translocates into the cell nucleus to regulate the transcription of numerous pro-memory transcription factors	[69-72]
NFAT	Memory CD4+ T cells	▪ Regulates transcription of genes that are critical for memory T cell development	[64]
NF-κB	Memory T cells	▪ Regulates transcription of genes that are critical for memory T cell development	[65]
RBPJ	Murine Carcinoma F9 cells	▪ Regulates chromatin domains and long-range chromatin interactions to maintain gene expression programs in transcriptional memory	[85]
Kinases
PKC-θ	T cells	▪ Key regulator of IL-2 expression (a critical cytokine for memory T cell development)	[58]
mTOR kinase	CD8+ T cell	▪ Regulates memory CD8 T-cell differentiation through the transcription factors T-bet and Eomesodermin.	[86,69]
Chromatin remodellers/RNA Pol II machinery/ncRNA/NPC
SWI/SNF	Yeast	▪ Prevents ISWI-based enzymes from erasing transcriptional memory	[5]
Nuclear Pore Proteins (Nup100)	Yeast	▪ Nup100 interacts with the promoter for yeast gene INO1 to regulate transcriptional memory.	[82]
piRNAs	C.Elegans	▪ Regulate a multigenerational epigenetic inheritance mechanism.	[87]

ncRNA = non coding RNA; NPC = Nuclear Pore Complex.