Calvo Ezequiel, Grzenda Adrienne, Lomberk Gwen, Mathison Angela, Iovanna Juan, Urrutia Raul
Laboratory of Epigenetics and Chromatin Dynamics, Mayo Clinic, Rochester, MN 55905, USA.
BMC Mol Biol. 2014 May 25;15:10. doi: 10.1186/1471-2199-15-10.
Krüppel-like factors (KLFs) are a group of master regulators of gene expression conserved from flies to human. However, scant information is available on either the mechanisms or functional impact of the coupling of KLF proteins to chromatin remodeling machines, a deterministic step in transcriptional regulation.
In the current study, we use genome-wide analyses of chromatin immunoprecipitation (ChIP-on-Chip) and Affymetrix-based expression profiling to gain insight into how KLF11, a human transcription factor involved in tumor suppression and metabolic diseases, works by coupling to three co-factor groups: the Sin3-histone deacetylase system, WD40-domain containing proteins, and the HP1-histone methyltransferase system. Our results reveal that KLF11 regulates distinct gene networks involved in metabolism and growth by using single or combinatorial coupling events.
This study, the first of its type for any KLF protein, reveals that interactions with multiple chromatin systems are required for the full gene regulatory function of these proteins.
Krüppel样因子(KLFs)是一组从果蝇到人类保守的基因表达主要调节因子。然而,关于KLF蛋白与染色质重塑机器偶联的机制或功能影响,这一转录调控中的决定性步骤,目前可用信息很少。
在本研究中,我们使用全基因组染色质免疫沉淀分析(芯片上的ChIP)和基于Affymetrix的表达谱分析,以深入了解参与肿瘤抑制和代谢疾病的人类转录因子KLF11如何通过与三个辅助因子组偶联发挥作用:Sin3-组蛋白去乙酰化酶系统、含WD40结构域的蛋白和HP1-组蛋白甲基转移酶系统。我们的结果表明,KLF11通过单一或组合偶联事件调节参与代谢和生长的不同基因网络。
这项针对任何KLF蛋白的同类研究中的首次研究表明,这些蛋白的完整基因调控功能需要与多个染色质系统相互作用。