Sequential chromatin immunoprecipitation to detect SUMOylated MeCP2 in neurons

• SUMO is a short peptide that can be covalently linked to proteins.
• SUMOylation is an essential post-translational modification.
• MeCP2 is a chromatin regulator whose mutations lead to Rett syndrome.
• Methodology to detect SUMOylated MeCP2 at specific genomic regions in neurons.

The small ubiquitin-like modifier (SUMO) is a short peptide that can be covalently linked to proteins altering their function. SUMOylation is an essential post-translational modification (PTM). Because of its dynamic nature, low abundance levels, and technical limitations, the occupation of endogenous SUMOylated transcription factors at genomic loci is challenging to detect. The chromatin regulator Methyl CpG binding protein 2 (MeCP2) is subjected to PTMs including SUMO. Mutations in MeCP2 lead to Rett syndrome, a severe neurodevelopmental disorder. Here, we present an efficient method to perform sequential chromatin immunoprecipitation (Seq-ChIP) for detecting SUMOylated MeCP2 in neurons. This Seq-ChIP technique is a useful tool to determine the occupancy of SUMOylated transcription and chromatin factors at specific genomic regions.