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Abnormal Histone Modification Patterns in Lupus CD4+ T Cells NAN HU, XIANGNING QIU, YONGQI LUO, JUN YUAN, YAPING LI, WENZHI LEI, GUIYING ZHANG, YING ZHOU, YUWEN SU, and QIANJIN LU
ABSTRACT. 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 EpiQuikTM 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). Conclusion. Histone modifications appear abnormal in CD4+ T cells in SLE. (First Release April 1 2008; J Rheumatol 2008;35:804-10) Key Indexing Terms:
HISTONE
From the Epigenetic Research Center and Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China. Supported by the National Natural Science Foundation of China (No. 30730083 and No. 30671883), Hunan Natural Science Foundation (No. 06C0049), and The Science Foundation of Hunan Province (No. 06SK3033). N. Hu, MD, PhD student; X. Qiu, MD, PhD student; Y. Luo, MD, PhD student; Y. Li, MD, Research Fellow; J. Yuan, MD, Research Fellow; W. Lei, MD, Research Fellow; G. Zhang, MD, Associate Professor; Y. Zhou, MD, Associate Professor; Y. Su, MD, Professor, Department of Dermatology; Q. Lu, MD, PhD, Director, Epigenetic Research Center, Professor, Chair, Department of Dermatology, Second Xiangya Hospital, Central South University. Address reprint requests to Dr. Q. Lu, Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, 410011, China. E-mail: qianlu@med.umich.edu Accepted for publication December 17, 2007. |
