Epigenetic transcriptional regulation by the nuclear factor Ikappab-zeta

转录因子NF-kappaB在微生物感染时对致炎细胞因子和抗菌蛋白的表达起着至关重要的作用。IkappaB-Zeta是一种核蛋白，是表达一组核转录因子-kappaB-靶基因所必需的。在本研究中，我试图阐明IIkappaB-Zeta在染色质背景下的转录调控。我发现，两个基因的表达都是由脂多糖和糖皮质激素协同诱导的，这两个基因都编码抗微生物蛋白。我指定了负责这两种刺激剂转录激活的顺式元件，并发现在刺激时，核因子-kappaB、糖皮质激素受体和染色质重塑因子以Ikappab-Zeta依赖的方式与顺式元件协同作用。

The transcription factor NF-kappaB is essential for expression of proinflammatory cytokines and antimicrobial proteins upon microbial infection. IkappaB-zeta is a nuclear protein required for expression of a subset of NF-kappaB-target genes. In the present study, I attempted to elucidate transcriptional regulation by IIkappaB-zeta in the chromatin context. I found that expression of two genes, both encoding antimicrobial proteins, was synergistically induced by lipopolysaccharide and glucocorticoid. I specified cis-elements responsible for the transcriptional activation by the two stimulants, and revealed that upon stimulation NF-kappaB, glucocorticoid receptor, and chromatin remodeling factors cooperatively associate with the cis-elements in an Ikappab-zeta-dependent manner.