Fig. 2

Epigenetic modifications can occur at different levels, including chromatin remodeling, histone modification, DNA methylation, transcription factor binding, and epitranscriptomic regulation of mRNAs and ncRNAs. a Chromatin remodeling is mediated by ATP-dependent complexes, such as brahma-associated factor (BAF), inositol requiring 80 (INO80), and imitation switch (ISWI), which could alter DNA accessibility. b Histone acetylation is balanced between "writer" enzymes, such as MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60), cAMP-response element binding protein-binding proteins (CBP), general control non-repressed 5 protein-related N-acetyltransferases (GNAT), and proto-oncogene tyrosine-protein kinase Src (SRC) protein families, and "erasers", such as HDAC and silent mating type information regulation 2 homolog 1 (SIRT) family proteins. Histone acetylation can be recognized by "readers", such as the BET family, which are associated with transcriptional activation. c Histone methylation is maintained by writers, such as SET, disruptor of telomeric silencing 1-like (DOT1L), and myeloid/lymphoid leukemia (MLL) protein families, and erasers such as lysine-specific demethylase (LSD) and Jumonji C domain-containing (JMJD) families. Histone methylation could be recognized by readers, such as plant homeodomain (PHD) finger proteins. d DNA methylation is regulated by DNMT and ten-eleven translocation (TET) proteins and can be recognized by readers such as methyl-CpG-binding domain protein 2 (MDB) and methyl CpG binding protein (MeCP). e Transcription factors (TFs) compete with nucleosomes for DNA access and could be recruited by various epigenetic modifiers. The interplay between transcription factors and epigenetic regulators is highly dynamic and complex, with TFs often working in concert with epigenetic modifiers to regulate gene expression. f Epitranscriptomic regulation of mRNAs and non-coding RNAs (ncRNAs), such as N⁶-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C) modification, play crucial roles in gene expression and cellular differentiation. RNA modifications can be recognized by reader proteins, such as YTH domain-containing proteins, which regulate mRNA stability, translation, and splicing. miRNP miRNA ribonucleoprotein complex, pre-miRNA precursor miRNA, pri-miRNA primary miRNA, HDAC histone deacetylase, BET bromodomain and extra-terminal motif protein, PCNA proliferating cell nuclear antigen, UHRF ubiquitin-like with PHD and ring finger domains, DNMT DNA methyltransferase, EZH2 enhancer of zeste homolog 2, SETDB SET domain bifurcated histone lysine methyltransferase, TCF-1 transcription factor 1, TOX thymocyte selection-associated high mobility group box, EOMES eomesodermin, NR4A nuclear receptor subfamily 4 group A, M nucleotide methylation, Me histone methylation, METLL methyltransferase-like family proteins, eIF3 eukaryotic translation initiation factor 3, YTHDC YTH domain containing, FTO fat mass and obesity-associated protein, ALKBH AlkB homolog, MEB methyl-CpG binding protein, Ago argonaute proteins