Histone H3k9 and H3k27 Acetylation Regulates IL-4/STAT6-Mediated Igε Transcription in B Lymphocytes

IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Ig epsilon 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 Ig epsilon promoter regions. Our results revealed that the Ig epsilon 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. Anat Rec, 298:1431-1439, 2015. (c) 2015 Wiley Periodicals, Inc.