TY - JOUR
T1 - CTCF-mediated functional chromatin interactome in pluripotent cells
AU - Handoko, Lusy
AU - Xu, Han
AU - Li, Guoliang
AU - Ngan, Chew Yee
AU - Chew, Elaine
AU - Schnapp, Marie
AU - Lee, Charlie Wah Heng
AU - Ye, Chaopeng
AU - Ping, Joanne Lim Hui
AU - Mulawadi, Fabianus
AU - Wong, Eleanor
AU - Sheng, Jianpeng
AU - Zhang, Yubo
AU - Poh, Thompson
AU - Chan, Chee Seng
AU - Kunarso, Galih
AU - Shahab, Atif
AU - Bourque, Guillaume
AU - Cacheux-Rataboul, Valere
AU - Sung, Wing Kin
AU - Ruan, Yijun
AU - Wei, Chia Lin
N1 - Funding Information:
We acknowledge the Genome Technology and Biology Group, particularly the sequencing team, for technical support. We also thank C. Xi and H.H. Ng who provided technical guidance for p300 ChIP optimization, M. Fullwood and B. Han for their 4C assay protocol, L.M. Hui and E. Cheung for 3C optimization and discussion, Z. Jingyao for BAC clone preparation and K. Zawack for reading the manuscript. This work was supported by the Agency for Science, Technology and Research (A*STAR), Singapore, and US National Institutes of Health (NIH) ENCODE grants (R01 HG004456-01, R01HG003521-01 and 1U54HG004557-01) to Y.R. and C.-L.W.
PY - 2011/7
Y1 - 2011/7
N2 - Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. However, little is known about CTCF-associated higher-order chromatin structures at a global scale. Here we applied chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, we identified 1,480 cis- and 336 trans-interacting loci with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements. This highly complex nuclear organization offers insights toward the unifying principles that govern genome plasticity and function.
AB - Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. However, little is known about CTCF-associated higher-order chromatin structures at a global scale. Here we applied chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, we identified 1,480 cis- and 336 trans-interacting loci with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements. This highly complex nuclear organization offers insights toward the unifying principles that govern genome plasticity and function.
UR - http://www.scopus.com/inward/record.url?scp=79959699992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959699992&partnerID=8YFLogxK
U2 - 10.1038/ng.857
DO - 10.1038/ng.857
M3 - Article
C2 - 21685913
AN - SCOPUS:79959699992
SN - 1061-4036
VL - 43
SP - 630
EP - 638
JO - Nature Genetics
JF - Nature Genetics
IS - 7
ER -