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 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.

Type II Interleukin-4 Receptor Activation in Basal Breast Cancer Cells Promotes Tumor Progression via Metabolic and Epigenetic Modulation

“…Previous evidence suggests that ACLY phosphorylation and activity regulate gene expression via histone acetylation in macrophages [17] and osteoclasts [38]. Moreover, IL4-driven histone acetylation is an important regulator of gene expression in B-lymphocytes [23] and macrophages [39,40], and the histone acetyltransferase P300/CBP is well recognized as an important mediator of IL4-stimulated gene regulation [41,42]. In our hands, IL4 treatment induced relatively small increases in total histone acetylation.…”

“…Our results indicated that lysates from IL4-treated cells were enriched in acetyl-lysine-positive histone H3 (Figure 4B). We then investigated specific acetylation marks that have been associated with IL4-mediated gene regulation [23]. Histones that were isolated from IL4-stimulated cell lines showed small increases in global acetylation of H3K9 and H3K27 acetylation compared with controls (Figure 4C).…”

Transcriptional landscape of the dorsal raphe serotonin neurons rendering stress resiliency

“…A possible mechanism to bridge this temporal gap is epigenetics, stable and long-lasting gene expression variations induced by non-DNA-encoded mechanisms such as DNA methylation, histone modification, and RNA modification 107,108 . It has been reported that STAT6 modulates both permissive and repressive histone modifications like H3K27ac, H3K9ac, and H3K27me3 101,109 . Considering that numerous studies have suggested a relationship between these histone modifications and the pathophysiology of depression 110,111 , further investigation of these histone modifications in the DRN serotonin neurons in a cell-type selective manner will provide insights into the complete picture of how antidepressants induce chronic transcriptomic changes through transient activation of IL-4-STAT6 signaling by using chromatin profiling methods applicable for a small number of cells such as CUT&Tag 112 .…”

Friend or Foe? The fascinating Tudor-SN protein

“…Tudor-SN also acts as a transcriptional coactivator of PPARc, a key transcription factor in adipocyte differentiation, and assists PPARc in promoting adipocyte differentiation and lipid droplet formation by enhancing histone acetylation [25]. In addition to binding to transcription factors, Tudor-SN can affect chromatin conformation and regulate gene transcription by recruiting the histone acetyltransferases GCN5 and CBP/p300 or the ATP-dependent chromatin remodeler SMARCA5 [16,25,[27][28][29][30][31].…”