Abstract
Protein methylation has an important role in the regulation of chromatin, gene expression and regulation. The protein methyl transferases are genetically altered in various human cancers. The enzymes that remove histone methylation have led to increased awareness of protein interactions as potential drug targets. Specifically, Lysine Specific Demethylases (LSD) removes methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been reported that LSD1 and its downstream targets are involved in tumor-cell growth and metastasis. Functional studies of LSD1 indicate that it regulates activation and inhibition of gene transcription in the nucleus. Here we made a discussion about the summary of histone lysine demethylase and their functions in various human cancers.
Highlights
Epigenetics refers to heritable changes regulating gene expression that are not a result of changes in the primary DNA sequence
Histone proteins are subjected to posttranslational modifications, like acetylation, methylation, phosphorylation, and ubiquitination, and these histone modifications act as the molecular switches that alter the state of compaction of chromatin to allow gene activation or repression [1,2,3]
Garcia Barcet etal reported that 80% of the promoters occupied by lysine-specifc demethylase 1 (LSD1) were bound to RNA polymerase II, suggesting that LSD1 was liked more in active genes rather than the inactive genes [64]
Summary
Epigenetics refers to heritable changes regulating gene expression that are not a result of changes in the primary DNA sequence. The tower domian is linked with the corepressor protein CoREST is essential for demethylation and removes methyl groups from monoand dimethyl Lys of histone H3, a gene activation mark [69] These enzymes are often deregulated in human diseases, it is essential to understand their physiological and pathological/biological functions by elucidating their exact structure, regulation and substrate specificity. Methylation-dependent ubiquitination is carried out by damage-specific DNA binding protein 1 (DDB1)/cullin (CUL4) E3 ubiquitin ligase complex and a DDB1-CUL4-associated factor 1 (DCAF1) adaptor, which recognizes monomethylated lysine residues and promotes polyubiquitylation of the other lysine residues on substrates such as retinoic acid related orphan nuclear receptor α (RORα) [153], stating that lysine methylation may destabilize target proteins through regulation of distant polyubiquitylation. These polyamine derivatives have been shown to modulate gene expression in breast cancer cells [176]
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