Single and combinatorial chromatin coupling events underlies the function of transcript factor krüppel-like factor 11 in the regulation of gene networks
1 Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, Canada
2 Laboratory of Epigenetics and Chromatin Dynamics, Mayo Clinic, Rochester, MN 55905, USA
3 INSERM U.624, Stress Cellulaire, 163 Avenue de Luminy, Case 915, Parc Scientifique et Technologique de Luminy, 13288 Marseille, Cedex 9, France
4 Translational Epigenomics Program, Center for Individualized Medicine (CIM), Mayo Clinic, Rochester, MN 55905, USA
5 Departments of Medicine, Physiology and Biochemistry, Mayo Clinic, 200 First Street SW, Guggenheim 10, Rochester, MN 55905, USA
BMC Molecular Biology 2014, 15:10 doi:10.1186/1471-2199-15-10Published: 25 May 2014
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.
Results and discussion
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.