Significant advances have been made in orthodontics and oral maxillofacial surgery for the diagnosis and treatment of dentofacial deformities. However, compared with bone, the effect of muscles of the craniofacial complex in the development of dentofacial deformities has received little attention. Recently, cellular and molecular studies of the musculoskeletal interactions have been used to investigate the etiology of dentofacial malocclusions. In this study, we tested for relationships that might exist between gene expression of the chromatin modifying enzymes histone deacetylase-4 (HDAC4) and histone acetyltransferase-4 (MYST4) and expression of myosin heavy chain (MyHC) genes and fiber-type percent occupancy (%Occ) in masseter muscle of patients undergoing orthognathic surgery to correct severe dentofacial malocclusions. The diagnostic categories of malocclusion in sagittal and vertical dimensions were: 1) Deep bite-Class II (D2); 2) Deep bite-Class III (D3); 3) Normal bite-Class II (N2); 4) Normal bite-Class III (N3), 5) Open bite-Class II (O2); 6) open bite with Class III (O3). Relative quantities (RQs) of gene expression were determined by reverse transcriptase real time polymerase chain reaction (RT-PCR) in RNA extracts of masseter samples, previously analyzed by immunohistochemistry for %Occ values. By multivariate analysis, RQs of HDAC4 and MYST4 expression did not differ significantly between malocclusion types. However, multiple high positive and negative correlations were found for HDAC4 and MYST4 with MyHC expression and with fiber type %Occ. Significant correlations occurred for HDAC4 with: IIX and neonatal MyHCs respectively in N2 and N3 subjects; fiber types I, I/II and neonatal/atrial %Occ respectively in D2 and N3, D2 and O3 subjects. Further investigations are needed to support evidence of these correlations and determine their significance toward diagnosis, treatment and relapse potential in the correction of dentofacial deformities. / Oral Biology