Table 1 Summary of epigenetic mechanisms and their role in memory cell development

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]