Genetics

Oral

Enhancer Connectome in Primary Human T Cells Reveals Target Genes of Autoimmune Disease-associated DNA Elements

Friday, June 16
4:00 PM - 4:15 PM

The imprecision of linking intergenic mutations to target genes has limited molecular understanding of diverse human diseases. Here, we show H3K27ac HiChIP generates high-resolution contact maps of active enhancers and target genes in rare primary human T cell subtypes. Differentiation of naïve T cells to either T helper 17 cells or regulatory T cells create subtype-specific enhancer-promoter interactions, specifically at regions of shared DNA accessibility. We provide an atlas for assigning molecular functions to autoimmune disease risk variants, linking hundreds of noncoding variants to putative gene targets. HiChIP target genes are supported by high-resolution CRISPR screens, expression quantitative trait loci, and allele-specific enhancer loops in patient-derived primary cells. The majority of disease-associated enhancers contact genes beyond the nearest gene in the linear genome, leading to a four-fold expansion of target genes for autoimmune diseases.

Ansuman Satpathy


Stanford University School Medicine

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Maxwell Mumbach

Stanford School of Medicine

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William Greenleaf

Asst Professor
Stanford Department of Genetics

William Greenleaf is an Assistant Professor in the Genetics Department at Stanford University School of Medicine, with a courtsey appointment in the Applied Physics Department. His highly interdisciplinary research links molecular biology, computer science, and genomics methods, to understand how the physical state of the human genome controls gene regulation and biological state. His long-term goal is to unlock an understanding of the physical “regulome” — i.e. the factors that control how the genetic information is read into biological instructions in health and disease.

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Howard Chang

Stanford School of Medicine

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