Fig. 1
From: The role of cigarette smoke-induced epigenetic alterations in inflammation
Epigenetic mechanisms. a DNA methylation. DNA methylation is catalyzed by DNA methyl transferases (DNMTs). DNA methylation involves the covalent transfer of a methyl group from S-adenosyl methionine (SAM) to 5′ position of cytosine residues in CG dinucleotides. DNA demethylation involves ten-eleven translocation (TET) proteins. TETs initiate DNA demethylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). 5fC and 5caC can be recognized and excised by thymine DNA glycosylase (TDG), and the residual abasic site is repaired as unmodified C by base excision repair (BER) pathway to complete “active” demethylation. Furthermore, oxygen and Fe(II) are indispensable for the TET enzymes to perform the successive oxidation of 5mC, 5hmC and 5fC. b Histone posttranscriptional modifications. Histone modification is regulated by opposing enzymes. Histone acetylation is mediated by histone acetyltransferases (HATs) and deacetylation by histone deacetylases (HDACs). Methylation is mediated by histone methyltransferase (HMTs) and demethylation by histone demethylases (HDMs). Phosphorylation is mediated by phosphorylase kinases (PKs). Ubiquitination is carried out through three main enzymatic reactions performed stepwise by ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3) consecutively; deubiquitination is mediated by deubiquitinating enzymes (DUBs). c The biogenesis of miRNA and lncRNA. The miRNA is transcribed to create the primary miRNA (pri‐miRNA) by RNA polymerase II (RNAPII). Following cleaved by the Drosha and DRCG8, precursor miRNA (pre‐miRNA) is exported from the nucleus by exportin 5. Then, Dicer and TAR RNA‐binding protein (TRBP) will further process the molecule and form a double-stranded miRNA: miRNA duplex. One strand of the duplex, together with the argonaute (AGO) protein and the target messenger RNA, is incorporated in the RNA-induced silencing complex (RISC) and subsequently targets mRNAs for degradation or translational repression. The lncRNA is transcribed mostly by RNAPII and its biogenesis process is similar to miRNA