Defining the landscape of chromatin-associated RNAs at human centromeric repeats

Centromeres are a specialized chromatin domain that are required for the assembly of the mitotic kinetochore and the accurate segregation of chromosomes. Non-coding RNAs play essential roles in regulating genome organization including at the unique chromatin environment present at human centromeres. To identify RNAs that regulate centromeres we performed Chromatin-Associated RNA sequencing (ChAR-seq) in three different human cell lines to generate a comprehensive list of RNAs associated with centromeric chromatin at a repeat array and chromosome-specific resolution. Centromere enriched RNAs display distinct contact behaviors across repeat arrays and generally belong to three categories: centromere encoded, nucleolar localized, and highly abundant, broad-binding RNAs. Most centromere encoded RNAs remain locally associated with their transcription locus with the exception of a subset of human satellite RNAs. These findings highlight the localized nature of higher order repeat derived RNAs and the diversity of RNA-DNA contact patterns at human centromeres that may reflect or contribute to local chromatin differences.