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IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Ige 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 Ige promoter regions. Our results revealed that the Ige 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.

The current study will investigate the mechanosensory-signaling pathway leading to STAT6 gene transcription in mouse cortical collecting duct epithelial cells. Many stimulants are capable of activating STAT6 in the kidney, but it is still unknown how STAT6 is directed to specific gene targets. In several cases, transcription co-factors, such as a fragment of polycystin 1, have been found to enter the nucleus along with STAT6 dimers. Additionally, the mechanism by which STAT6 becomes activated by mechanosensation is currently unknown. A primary goal of this study is to determine the kinase involved in STAT6 phosphorylation (activation) in changing flow conditions. The STAT family has cell-type specific promoter binding sites. Common STAT controlled cis-regulatory modules (cSCCs) are cis-regulatory modules (CRMs) that can be recognized by all STAT family members across cell types. 116 cSCCs have been identified and correspond to JAK/STAT signaling genes. I hypothesize that different stimulants (cytokines vs...

Three hundred million individuals are at risk of infection by schistosomes, which cause severe kidney and liver disease, and 280 000 deaths annually. Infection levels are mainly under the control of a major locus, SM1 (Schistosoma mansoni 1), mapped in 5q31q33 region. An association between the rs1800925 polymorphism in the IL13 promoter and infection levels was detected. Subjects bearing the rs1800925T/T genotype were much less infected than individuals with other genotypes. We went on to investigate whether other polymorphisms in genes involved in the TH2 cytokine immune response could affect susceptibility to schistosome infection. An association between STAT6 rs324013 polymorphism and infection levels was also found. These two polymorphisms which have an additive effect were not strongly correlated with any other tested markers surrounding the two genes. Moreover, these polymorphisms affect transcription factor binding to the promoter regions. These results are consistent with the TH2 cytokine pathway enhancing resistance to schistosome infection. Key concepts: IL13 gene is associated to the control of infection levels in schistosomiasis. STAT6 gene is associated to the control of infection levels in schistosomiasis. IL13 and STAT6 polymorphisms have synergic effect. Keywords: schistosomiasis; infection; IL13; STAT6; gene; parasitic