The nanoCUT&RUN technique visualizes telomeric chromatin in Drosophila

Advances in genomic technology lead to a more focused pattern for the
distribution of chromosomal proteins and a better understanding of their
functions. The recent development of the CUT&RUN technique marks
one of the important such advances. Here we develop a modified
CUT&RUN technique that we termed nanoCUT&RUN, in which a
high affinity nanobody to GFP is used to bring micrococcal nuclease to the
binding sites of GFP-tagged chromatin proteins. Subsequent activation of
the nuclease cleaves the chromatin, and sequencing of released DNA
identifies binding sites. We show that nanoCUT&RUN efficiently
produces high quality data for the TRL transcription factor in Drosophila
embryos, and distinguishes binding sites specific between two TRL
isoforms. We further show that nanoCUT&RUN dissects the
distributions of the HipHop and HOAP telomere capping proteins, and
uncovers unexpected binding of telomeric proteins at centromeres.
nanoCUT&RUN can be readily applied to any system in which a
chromatin protein of interest, or its isoforms, carries the GFP
tag.