Abnormal histone modification patterns in lupus CD4+ T cells.
OBJECTIVE
To investigate alterations in histone modifications in patients with systemic lupus erythematosus (SLE).


METHODS
Global histone H3/H4 acetylation and H3K4/H3K9 methylation in CD4+ T cells from 20 SLE patients and 10 healthy control subjects were assayed using the EpiQuik global histone H3/H4 acetylation and H3K4/H3K9 methylation assay kits. mRNA levels of 12 members of 3 classes of chromatin modifier genes were measured by real-time quantitative polymerase chain reaction.


RESULTS
Global histone H3 and H4 hypoacetylation was observed in active lupus CD4+ T cells compared with controls (p = 0.002 and p = 0.009, respectively). The degree of histone H3 acetylation correlated negatively with increased disease activity in lupus patients as measured by SLEDAI (r = -0.889, p = 0.044). We found global histone H3K9 hypomethylation in both active and inactive lupus CD4+ T cells, compared with controls (p = 0.001, p = 0.003, respectively). However, global levels of H3K4 methylation were not different between patients and controls. SIRT1 mRNA levels were significantly increased in active lupus CD4+ T cells compared with controls (p < 0.001), while mRNA levels of CREBBP, P300, HDAC2, HDAC7, SUV39H2, and EZH2 were significantly downregulated in patients with active lupus (p < 0.001, p < 0.001, p = 0.01, p < 0.001, p = 0.003, p = 0.001, respectively).


CONCLUSIONS
Histone modifications appear abnormal in CD4+ T cells in SLE.
Hu
Nan
N
Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China.
Qiu
Xiangning
X
Luo
Yongqi
Y
Yuan
Jun
J
Li
Yaping
Y
Lei
Wenzhi
W
Zhang
Guiying
G
Zhou
Ying
Y
Su
Yuwen
Y
Lu
Qianjin
Q
D000107:Acetylation; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D011496:Protein Methyltransferases; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism
D006657:Histones; D012333:RNA, Messenger; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases