title: Histone H3k9 and H3k27 Acetylation Regulates IL-4/STAT6-Mediated Igε Transcription in B Lymphocytes.
abstract: IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Igε via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Igε promoter regions. Our results revealed that the Igε gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xinting
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.|Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China.|Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, China.|Department of Physiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: He
mesh_terms: D000107:Acetylation; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D004195:Disease Models, Animal; D004720:Endonucleases; D005786:Gene Expression Regulation; D006657:Histones / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010047:Ovalbumin; D000072670:PTB-Associated Splicing Factor; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D016601:RNA-Binding Proteins / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D006657:Histones; C508598:IL4 protein, human; D007139:Immunoglobulin epsilon-Chains; D009687:Nuclear Proteins; D000072670:PTB-Associated Splicing Factor; D016601:RNA-Binding Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D010047:Ovalbumin; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; D004720:Endonucleases; C095221:SND1 protein, human
keywords: IL-4; Igε; STAT6; histone modification