CTCF is a ubiquitously expressed regulator of fundamental genomic processes 
including transcription, intra- and interchromosomal interactions, and chromatin 
structure. Because of its critical role in genome function, CTCF binding 
patterns have long been assumed to be largely invariant across different 
cellular environments. Here we analyze genome-wide occupancy patterns of CTCF by 
ChIP-seq in 19 diverse human cell types, including normal primary cells and 
immortal lines. We observed highly reproducible yet surprisingly plastic genomic 
binding landscapes, indicative of strong cell-selective regulation of CTCF 
occupancy. Comparison with massively parallel bisulfite sequencing data 
indicates that 41% of variable CTCF binding is linked to differential DNA 
methylation, concentrated at two critical positions within the CTCF recognition 
sequence. Unexpectedly, CTCF binding patterns were markedly different in normal 
versus immortal cells, with the latter showing widespread disruption of CTCF 
binding associated with increased methylation. Strikingly, this disruption is 
accompanied by up-regulation of CTCF expression, with the result that both 
normal and immortal cells maintain the same average number of CTCF occupancy 
sites genome-wide. These results reveal a tight linkage between DNA methylation 
and the global occupancy patterns of a major sequence-specific regulatory 
factor.