Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" (IGB), CNR, 80131 Naples, Italy.
PPAR Res. 2010;2010. doi: 10.1155/2010/409168. Epub 2010 Sep 8.
Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most extensively studied ligand-inducible transcription factors (TFs), able to modulate its transcriptional activity through conformational changes. It is of particular interest because of its pleiotropic functions: it plays a crucial role in the expression of key genes involved in adipogenesis, lipid and glucid metabolism, atherosclerosis, inflammation, and cancer. Its protein isoforms, the wide number of PPARγ target genes, ligands, and coregulators contribute to determine the complexity of its function. In addition, the presence of genetic variants is likely to affect expression levels of target genes although the impact of PPARG gene variations on the expression of target genes is not fully understood. The introduction of massively parallel sequencing platforms-in the Next Generation Sequencing (NGS) era-has revolutionized the way of investigating the genetic causes of inherited diseases. In this context, DNA-Seq for identifying-within both coding and regulatory regions of PPARG gene-novel nucleotide variations and haplotypes associated to human diseases, ChIP-Seq for defining a PPARγ binding map, and RNA-Seq for unraveling the wide and intricate gene pathways regulated by PPARG, represent incredible steps toward the understanding of PPARγ in health and disease.
过氧化物酶体增殖物激活受体 γ（PPARγ）是研究最广泛的配体诱导转录因子（TFs）之一，能够通过构象变化调节其转录活性。它之所以特别有趣，是因为它具有多种功能：它在脂肪生成、脂质和糖代谢、动脉粥样硬化、炎症和癌症中涉及的关键基因的表达中起着至关重要的作用。其蛋白质同工型、大量的 PPARγ 靶基因、配体和共调节因子有助于确定其功能的复杂性。此外，遗传变异的存在可能会影响靶基因的表达水平，尽管 PPARG 基因变异对靶基因表达的影响尚未完全了解。大规模平行测序平台的引入——在下一代测序（NGS）时代——彻底改变了研究遗传疾病遗传原因的方式。在这种情况下，用于识别 PPARG 基因编码和调控区域内与人类疾病相关的新核苷酸变异和单倍型的 DNA-Seq、用于定义 PPARγ 结合图谱的 ChIP-Seq 以及用于揭示由 PPARG 调节的广泛而复杂的基因途径的 RNA-Seq，代表了朝着理解健康和疾病中的 PPARγ 迈出的令人难以置信的步骤。
