SINHCAF, a previously unknown link between HIF and NF-kappaB signalling

NF-kappaB转录因子家族的激活形成了生物体抵御环境威胁的第一道防线之一，并有助于编程适当的细胞反应。类似地，缺氧诱导因子（HIF）是响应环境氧的变化并协调转录程序的转录因子家族，其形成细胞对缺氧环境的响应的重要部分。一些证据表明，NF-κ B和HIF途径是内在联系的。SINHCAF（Sin 3A，HDAC Associated Factor）是一种相对未知的蛋白质，最初被命名为FAM 60 A。几个小组的工作导致了它的新名字，因为它被鉴定为与Sin 3A-HDAC转录调节因子复合物相关的蛋白质。SINHCAF已被证明控制干细胞生物学，并在分化的细胞中调节细胞周期，增殖和迁移。尽管有这些发现，很少有人知道SINHCAF，以及它是如何能够执行其生物学functions.Published和未出版的工作，从监督小组已经证明，SINHCAF控制HIF和NF-κ B转录活性。SINHCAF占据并调节大量NF-κ B和HIF靶基因，通过全基因组染色质免疫沉淀结合下一代测序（ChIP-seq）和RNA-seq进行评估（图1）。这些数据定义了SIHCAF和HIF/NF-κ B信号之间以前未知的调节联系。在这个项目中，学生将研究SINHCAF调节NF-κ B和HIF的机制。

Activation of the NF-kappaB transcription factor family forms one of the first lines of defence against environmental threats to the organism and helps programme an appropriate cellular response. Similarly, Hypoxia Inducible Factors (HIFs) are a family of transcription factors that respond to changes in environmental oxygen and orchestrate a transcriptional program, which forms an important part of the cellular response to a hypoxic environment. Several lines of evidence have demonstrated that the NF-kappaB and HIF pathways are intrinsically linked. Both transcription factors play an important role in processes associated with inflammation and hypoxia, two stresses closely linked with accelerated ageing and decreased healthspan.SINHCAF (Sin3A, HDAC Associated Factor), is a relatively unknown protein, originally named as FAM60A. Work from several groups has led to its new name since being identified as a protein associated with the Sin3A-HDAC transcriptional regulator complex. SINHCAF has been shown to control stem cell biology, and in differentiated cells it regulates the cell cycle, proliferation and migration. Despite these findings, very little is known about SINHCAF and how it is able to perform its biological functions.Published and unpublished work from the supervisory team has demonstrated that SINHCAF controls both HIF and NF-kappaB transcriptional activity. SINHCAF occupies and regulates a vast number of NF-kappaB and HIF target genes assessed by genome wide Chromatin Immunoprecipitation coupled to next generation Sequencing (ChIP-seq) and RNA-seq (Figure 1). This data defines a previously unknown regulatory link between SIHCAF and HIF/NF-kappaB signalling.In this project the student will investigate the mechanism behind SINHCAF regulation of NF-kappaB and HIF.