Research Article Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity Jun Lu, 1 Xiaoli Zhang, 1 Tingting Shen, 1 Chao Ma, 2 Jun Wu, 1 Hualei Kong, 1 Jing Tian, 3 Zhifeng Shao, 1 Xiaodong Zhao, 1,2 and Ling Xu 2,4 1 Shanghai Center for Systems Biomedicine, School of Biomedical Engineering, State Key Laboratory on Oncogene and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China 2 Tumor Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China 3 College of Life Science, Northwest University, 229 Taibai Road, Xi’an 710069, China 4 Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai 200437, China Correspondence should be addressed to Ling Xu; xulq67@aliyun.com Received 2 November 2015; Revised 3 February 2016; Accepted 7 February 2016 Academic Editor: Ching-Liang Hsieh Copyright © 2016 Jun Lu et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment ( < 0.05). Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated), intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci. 1. Introduction Chromatin is the macromolecular complex of DNA and histone proteins that provides the scaffold for packaging the eukaryotic genome [1, 2]. Histones H2A, H2B, H3, and H4 are the basic components of nucleosomes, which form the fundamental unit of chromatin [3, 4]. Chemical modifications to the histones alter chromatin structure and regulate gene expression by altering noncovalent interactions within and between nucleosomes [2, 5]. H3K4Me3 is an active histone modification which is positively associated with gene expression [3, 6]. Previous studies have shown that the levels of H3K4Me3 modification are closely associated with the development, treatment, and diagnosis of disease [7–9]. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has been developed to systematically characterize the contribution of epigenetic regulation in various biological processes via genome-wide profiling of various chemical modifications of histone proteins and genomic DNA methylation [10]. Lung cancer has become the leading cause of cancer- related deaths worldwide [11]. Overall, only 16.8% of patients with lung cancer survive five years aſter their first definite diagnosis, mainly as a consequence of uncontrollable cell proliferation or tumor metastasis [12, 13]. Although various therapeutic interventions, including surgery, chemotherapy, and radiotherapy, have been developed to prolong the sur- vival time of patients, drug side effects, pain, and emaciation Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2016, Article ID 7276161, 13 pages http://dx.doi.org/10.1155/2016/7276161