1. CTCF-mediated functional chromatin interactome in pluripotent cells
- Author
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Lusy Handoko, Yubo Zhang, Han Xu, Galih Kunarso, Eleanor Wong, Guoliang Li, Marie Schnapp, Chaopeng Ye, Yijun Ruan, Guillaume Bourque, Elaine G.Y. Chew, Chew Yee Ngan, Chia-Lin Wei, Charlie Wah Heng Lee, Wing-Kin Sung, Joanne Lim Hui Ping, Fabianus Hendriyan Mulawadi, Jianpeng Sheng, Valere Cacheux-Rataboul, Chee Seng Chan, Atif Shahab, and Thompson Poh
- Subjects
Epigenomics ,Pluripotent Stem Cells ,CCCTC-Binding Factor ,Chromatin Immunoprecipitation ,Transcription, Genetic ,Computational biology ,Biology ,insulator ,Interactome ,Article ,epigenetic regulation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Enhancer binding ,Genes, Regulator ,Genetics ,Animals ,Epigenetics ,RNA, Small Interfering ,Promoter Regions, Genetic ,Cells, Cultured ,In Situ Hybridization, Fluorescence ,030304 developmental biology ,0303 health sciences ,Embryo, Mammalian ,Chromatin ,DNA-Binding Proteins ,Repressor Proteins ,Gene Expression Regulation ,CTCF ,Nuclear lamina ,enhancer ,Chromatin immunoprecipitation ,030217 neurology & neurosurgery ,nuclear lamina ,chromatin organization - Abstract
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.
- Published
- 2011