Biophysical Society Thematic Meeting| Santa Cruz 2018

Genome Biophysics: Integrating Genomics and Biophysics to Understand Structural and Functional Aspects of Genomes

Poster Abstracts

21-POS Board 21 CTCF-mediated Genome Organization Distinguishes Primary Human Erythroid Cells Y. Ada Zhan 1 , Liuyang Cai 1 , Vincent Schulz 2 , Patrick Gallagher 2 , Yijun Ruan 1 , Jeff Chuang 1 . 1 The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA, 2 Yale University, New Haven, CT, USA. Although they share the same genome, the hundreds of cell types in the human body have distinct gene expression profiles. Genome organization plays an important role in bringing distal regulatory elements, such as enhancers, and promoters into proximity in support of cell type specific expression. CTCF has been found essential in mediating chromatin interactions and higher order spatial chromosome folding, and CTCF binding sites usually mark the boundaries of topologically associated domains (TADs). Moreover mounting evidence has revealed the indispensable roles of CTCF at sub-TAD level in segregating enhancer usage or bringing enhancers to their targets in a cell type specific manner. In this study, we investigated how CTCF regulates erythroid gene expression in comparison with B cells and T cells. We found that CTCF binding and CTCF-mediated interactions are elevated at promoter regions (TSS ±5kb) of up- regulated genes in erythroid cells. Although the binding and interactions of CTCF are weaker at cell type-specific than constitutive loci, the erythroid-specific interactions have significant associations with erythroid GWAS SNPs and with erythroid-specific genes. For example, SNP rs2703485 was found in an anchor of an erythroid CTCF loop linking enhancers to the KIT promoter, and it is also bridged to rs218264 and rs218265 via another erythroid CTCF loop. The C and T allele were found solely at rs2703485 and rs218265 sites respectively in our erythroid CTCF ChIA-PET experiment, suggesting this allele is necessary for loop formation. Interestingly, at rs2703485 the C allele is only dominant in the 1000 genomes AFR population. Previous GWAS studies have concluded that the three SNPs have association with red cell phenotype like mean corpuscular volume. Herein we showed they are topologically linked together via CTCF loops and regulate KIT expression.

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