Nominally replicated SNP association signals in the KDM3B and KDM4C genes are also of potential interest. Both genes function to demethylate Lysine 9 at histone 3 (H3K9).[49] Methylation state of this histone tail site plays a role in silencing/activating HIV transcription at the 5’ end of the long terminal repeats: H3K9 sites are highly methylated in silenced latent HIV, generating a reservoir of virus that is unaffected by the immune system and highly active antiretroviral therapy (HAART).[50] Reactivation of HIV transcription is accompanied by a drop in trimethylation of H3K9,[50] and KDM4C is known to convert trimethylated to dimethylated histone residues.[49]
