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 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. Anat Rec, 298:1431–1439, 2015. © 2015 Wiley Periodicals, Inc.