RT Journal
A1 Wang, Hao
A1 Maurano, Matthew T.
A1 Qu, Hongzhu
A1 Varley, Katherine E.
A1 Gertz, Jason
A1 Pauli, Florencia
A1 Lee, Kristen
A1 Canfield, Theresa
A1 Weaver, Molly
A1 Sandstrom, Richard
A1 Thurman, Robert E.
A1 Kaul, Rajinder
A1 Myers, Richard M.
A1 Stamatoyannopoulos, John A.
T1 Widespread plasticity in CTCF occupancy linked to DNA methylation
JF Genome Research 
JO Genome Research 
YR 2012 
FD September 01 
VO 22 
IS 9 
SP 1680 
OP 1688 
DO 10.1101/gr.136101.111 
UL http://genome.cshlp.org/content/22/9/1680.abstract 
AB 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.