Centromeres are characterized by the centromere-specific H3 variant CENP-A, 
which is embedded in chromatin with a pattern characteristic of active 
transcription that is required for centromere identity. It is unclear how 
centromeres remain transcriptionally active despite being flanked by repressive 
pericentric heterochromatin. To further understand centrochromatin's response to 
repressive signals, we nucleated a Polycomb-like chromatin state within the 
centromere of a human artificial chromosome (HAC) by tethering the 
methyltransferase EZH2. This led to deposition of the H3K27me3 mark and PRC1 
repressor binding. Surprisingly, this state did not abolish HAC centromere 
function or transcription, and this apparent resistance was not observed on a 
noncentromeric locus, where transcription was silenced. Directly tethering the 
reader/repressor PRC1 bypassed this resistance, inactivating the centromere. We 
observed analogous responses when tethering the heterochromatin Editor 
Suv39h1-methyltransferase domain (centromere resistance) or reader HP1α 
(centromere inactivation), respectively. Our results reveal that the HAC 
centromere can resist repressive pathways driven by H3K9me3/H3K27me3 and may 
help to explain how centromeres are able to resist inactivation by flanking 
heterochromatin.