Epigenetic influence of KAT6B and HDAC4 in the development of skeletal malocclusion.
BACKGROUND
Genetic influences on the development of malocclusion include heritable effects on both masticatory muscles and jaw skeletal morphology. Beyond genetic variations, however, the characteristics of muscle and bone are also influenced by epigenetic mechanisms that produce differences in gene expression. We studied 2 enzymes known to change gene expressions through histone modifications, chromatin-modifying histone acetyltransferase KAT6B and deacetylase HDAC4, to determine their associations with musculoskeletal variations in jaw deformation malocclusions.


METHODS
Samples of masseter muscle were obtained from subjects undergoing orthognathic surgery from 6 malocclusion classes based on skeletal sagittal and vertical dysplasia. The muscles were characterized for fiber type properties by immunohistochemistry, and their total RNA was isolated for gene expression studies by microarray analysis and quantitative real-time polymerase chain reaction.


RESULTS
Gene expressions for fast isoforms of myosins and contractile regulatory proteins and for KAT6B and HDAC4 were severalfold greater in masseter muscles from a patient with a deepbite compared with one with an open bite, and genes related to exercise and activity did not differ substantially. In the total population, expressions of HDAC4 (P = 0.03) and KAT6B (P = 0.004) were significantly greater in subjects with sagittal Class III than in Class II malocclusion, whereas HDAC4 tended to correlate negatively with slow myosin type I and positively with fast myosin gene, especially type IIX.


CONCLUSIONS
These data support other published reports of epigenetic regulation in the determination of skeletal muscle fiber phenotypes and bone growth. Further investigations are needed to elucidate how this regulatory model might apply to musculoskeletal development and malocclusion.
Private practice, Teaneck, NJ.
Ahrin
A
Huh
Michael J
MJ
Horton
Karen T
KT
Cuenco
Gwenael
G
Raoul
Anthea M
AM
Rowlerson
Joel
J
Ferri
James J
JJ
Sciote
D057890:Epigenomics; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008312:Malocclusion, Angle Class II / Q000235:genetics; D008313:Malocclusion, Angle Class III / Q000235:genetics; D008406:Masseter Muscle / Q000187:drug effects*; D009218:Myosins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D024343:Open Bite / Q000235:genetics*; D057887:Overbite / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics* / Q000494:pharmacology; D055815:Young Adult
D012097:Repressor Proteins; D051548:Histone Acetyltransferases; C487137:KAT6B protein, human; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D009218:Myosins