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LSD1

 

 

Lysine specific histone demethylase 1 (LSD1, also known as KDMA1) is an epigenetic “eraser”. LSD1 removes chemical groups, known as methyl marks, from protein-DNA structures known as nucleosomes. Nucleosomes comprise DNA wrapped around structural proteins called histones. Histones, like most proteins, contain an amino acid known as lysine, a particularly important amino acid for chemical modification. LSD1 specifically erases methyl marks at lysine 4 and lysine 9 (H3K4, H3K9, “K” is the symbol for lysine). Depending on the presence or absence of methyl marks, DNA assumes an “open” conformation available for transcription of genes, or DNA assumes a “closed” conformation blocking gene expression.

A methyl mark at H3K4 is associated with an open conformation of DNA, and LSD1 closes DNA by removing the methyl mark. In contrast, a methyl mark at H3K9 is associated with a closed conformation of DNA, and LSD1 opens DNA by removing the methyl mark. LSD1 can therefore both promote and block gene expression, and is unique as an epigenetic modifier in this respect. Finally, each lysine can have up to three methyl marks, and LSD1 is only capable of removing the first two marks. The number of methyl marks can also have an effect on gene expression.

LSD1II

LSD1’s major role in cancer has been elucidated. LSD1 acts in complex with cancerous proteins, “oncoproteins”, to disrupt the equilibrium of healthy cells and drive expression of a stem cell-like phenotype. This means cells that are differentiated, or designed to perform a tissue-specific function, revert to a more plastic, undefined state characterized by constant growth and invasion of nearby tissues. Importantly, as an epigenetic protein, LSD1 itself complexes with myriad other transcriptional co-activators and co-repressors, and can therefore influence cells on a much greater level than a typical individual protein. This makes LSD1 an attractive target for anti-tumor purposes.

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