The reported global hypermethylation of H3K9 in HD mouse models and in patients [132–135] has been explained as a result of abnormal increase of binding activity to the promoters of chromatin regulator genes: (i) the binding of Sp1 and Sp3 to the promoter of the histone-lysine N-methyltransferase SET (SU(VAR)3-9, enhancer of Zeste, Trithorax) domain bifurcated 1 (SETDB1, also known as ESET) [134] and (ii) the binding of caudal type homeobox 2 (Cdx2) to the promoter of the DNA-dependent ATPase/helicase alpha thalassemia/mental retardation X-linked (ATRX) [136]. Here, SETDB1 is linked to Huntington disease.