Biophysical characterization of the basic cluster in the transcription repression domain of human MeCP2 with AT-rich DNA

Highlights: • Basic cluster region (residues 295 to 313) in the MeCP2 binds to AT-rich DNA. • NMR relaxation data identified that IKKRKTRE is critical for binding. • Basic cluster peptide binds to the minor groove of DNA, similar to AT-hooks. MeCP2 is a chromatin associated protein which is highly expressed in brain and relevant with Rett syndrome (RTT). There are AT-hook motifs in MeCP2 which can bind with AT-rich DNA, suggesting a role in chromatin binding. Here, we report the identification and characterization of another AT-rich DNA binding motif (residues 295 to 313) from the C-terminal transcription repression domain of MeCP2 by nuclear magnetic resonance (NMR) and isothermal calorimetry (ITC). This motif shows a micromolar affinity to AT-rich DNA, and it binds to the minor groove of DNA like AT-hook motifs. Together with the previous studies, our results provide an insight into a critical role of this motif in chromatin structure and function.