The human genome is an over 2 meters long polymer DNA molecule that has to be folded extensively within the micrometer-sized nuclear space.How the genome is spatially organized has been an intriguing question.It is known CTCF is extensively involved in chromatin looping and compartmentalization.We performed Chromatin Interaction Analysis by Paired-End Tag Sequencing(ChIA-PET)assay on CTCF in human cell lines including GM12878,HeLa,MCF7 and K562,to reveal the chromatin folding principle mediated by CTCF and its functional relationship to transcription.The results indicate that chromatin interaction loops mediated by CTCF are pervasively identified across the human chromosomes,and the CTCF looping structure is largely conserved across distinct cell types.Mostly continuous CTCF loops partition the genome into contact domains.By studying the CTCF binding motif orientation at the CTCF loop anchor regions,we show that CTCF not only loops the chromatin in a convergent way,but also substantially in a tandem manner.Thus,we propose CTCF binding direction governed chromatin folding principles.When we overlay functional data,the results show RNAPII selectively utilizes the CTCF defined structure,and promoters are enriched at the CTCF loop anchors.We also performed haplotype-specificity analysis on the CTCF interaction loops in GM12878,and the results showed allele-specific CTCF looping was related to gene imprinting and X chromosome inactivation.Overall,our CTCF ChIA-PET data reveals that largely conserved CTCF mediated chromatin loops organize the human genome in a nonstochastic fashion,and CTCF interaction loops are structurally and functionally important for genome organization and regulation.