In vivo tissue-specific chromatin profiling in Drosophila v2

Chromatin regulation plays an essential role in many nuclear processes, and genome-wide chromatin profiling approaches contribute to understanding how chromatin regulates cell homeostasis. Chromatin dysregulation lies in the heart of many human diseases, which most of them have a tissue-specific nature. Because of the physiological similarity of Drosophila and humans, tissue-specific studies can be performed using fruit flies. Here, we present an improved nuclear tagging approach that allows for efficient purification of cell-type specific nuclei from Drosophila increasing yield and stringency. Using this protocol, we purified photoreceptor neuron nuclei, and demonstrate the feasibility and high quality of chromatin accessibility profiling as well as profiling of histones and histone modifications, using Omni-ATAC and ChIP-seq, respectively. Last, we describe a modification to the nuclei purification protocol that allows for application of recently developed CUT&Tag and demonstrate that CUT&Tag outperforms traditional ChIP-seq, although protocol might require further optimization.