Genome-wide histone methylation profile for heart failure.
Epigenetic alterations are implicated in the development of cardiac hypertrophy and heart failure, but little is known of which epigenetic changes in which regions of the genome play such a role. We now show that trimethylation of histone H3 on lysine-4 (K4TM) or lysine-9 (K9TM) is markedly affected in cardiomyocytes in association with the development of heart failure in a rat disease model. High-throughput pyrosequencing performed with ChIP products for K4TM or K9TM prepared from human left ventricular tissue with retained or damaged function also revealed that protein-coding genes located in the vicinity of K4TM marks differ between functional and disabled myocytes, yet both sets of genes encode proteins that function in the same signal transduction pathways for cardiac function, indicative of differential K4TM marking during the development of heart failure. However, K9TM mark-profile was less dependent on the disease status compared to that of K4TM. Our data collectively reveal global epigenetic changes in cardiac myocytes associated with heart failure.
Kaneda
Ruri
R
Functional Genomics, Jichi Medical University, Tochigi 329-0498, Japan.
Takada
Shuji
S
Yamashita
Yoshihiro
Y
Choi
Young Lim
YL
Nonaka-Sarukawa
Mutsuko
M
Soda
Manabu
M
Misawa
Yoshio
Y
Isomura
Tadashi
T
Shimada
Kazuyuki
K
Mano
Hiroyuki
H
D000368:Aged; D000818:Animals; D002135:Calcium-Binding Proteins; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D016000:Cluster Analysis; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl
D002135:Calcium-Binding Proteins; D006657:Histones; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D008239:Lysine