Sandbox Reserved 1491: Difference between revisions

Genes regulation is directly related to the condensation state of the chromatin. Indeed, chromatin can be in the form of heterochromatin (condensed form of DNA) or euchromatin (relaxed form of DNA) which correspond respectively to the transcriptionally silent and active forms of DNA. Chromatin is composed of DNA wrapped around histone octamers forming nucleosomes. The histone tails residues can be acetylated, methylated or demethylated by enzymes in order to modify chromatin state and therefore gene expression. Different types of proteins involved in this process exist, such as histone acetylase (HAT), histone methylase (HMT) or histone demethylase (HDM).

   

Two families of histone-lysine demethylases (KDM) have been identified as follows : the flavin (FAD) -dependent lysine-specific demethylases and the Fe(II)-dependent Jumonji C (JmjC) family. JmjC[1] is subfamily of histone demethylases which regroups several proteins containing a specific catalytic domain called Jmjc found in 2xml structure. KDM4 demethylases belong to the JmjC family and contains six members : KDM4A-F.

KDM4C/JMJD2 is a protein which converts specific trimethylated histone residues to the dimethylated form. Indeed, it catalyzes the demethylation of both histone H3 Lysine 9 (H3K9me3) and Lysine 36 (H3K36me3) by hydroxylation of the lysine methyl group leading to a dissociation of the methyl group from the lysine histone tail. KDM4C employs 2-oxoglutarate (OG), Fe2+ and oxygen as cosubstrates to promote its enzymatic reaction, thus the dissociation of methyl groups.