Krüppel-like factors, chromatin, and epigenetics: new frontiers in understanding the regulation of complex diseases

Abstract

The discovery of Krüppel-Like Factor (KLF) proteins has contributed more than one could have imagined regarding the mechanisms that underscore complex physiological and pathological phenotypes. From the start, our laboratory hypothesized that elucidating the intricate network of interactions between KLF transcription factors and epigenetic machinery would provide significant insight into the mechanisms of human diseases. Drawing from nearly two decades of data and utilizing a novel system biology approach, we propose the novel hypothesis that KLF proteins function as master transcription factors to deliver epigenetic information to an orchestra of gene promoters, influencing chromatin dynamics and global patterns of gene expression. Multidimensional comparison and visualization of robust experimental datasets using a paradigm transcription factor, KLF11, illustrate the complicated, yet delightful nature of the relationship between KLF proteins and their chromatin cofactors, providing exciting revelations into the causes, prognosis, and therapeutic management of complex diseases.