Unknown,Transcriptomics,Genomics,Proteomics

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ATAC-seq of a K562 cell line model with a patient-based t(3;8) translocation

ABSTRACT: Open chromatin regions were analyzed by ATAC-seq in t(3;8) K562 and wild type K562 to characterize the MYC super-enhancer region. ATAC-seq was performed as described (Buenrostro et al., 2013) with a modification in the lysis buffer to reduce mitochondrial DNA contamination.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Ruud Delwel

PROVIDER: E-MTAB-10785 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Objective: Although glucagon-secreting Î±-cells and insulin-secreting Î²-cells have opposing functions in regulating plasma glucose levels, the two cell types share a common developmental origin and have overlaps in their transcriptome and epigenome profiles. Notably, destruction of one of these cell populations can stimulate repopulation via transdifferentiation of the other cell type, at least in mice, suggesting plasticity between these cell fates. Furthermore, dysfunction of both Î±- and Î²-cells contributes to the pathophysiology of type 1 and type 2 diabetes, and Î²-cell de-differentiation has been proposed to contribute to type 2 diabetes. Our objective was to delineate the molecular properties that maintain islet cell type specification yet allow for cellular plasticity. We hypothesized that correlating cell type-specific transcriptomes with an atlas of open chromatin will identify novel genes and transcriptional regulatory elements such as enhancers involved in Î±- and Î²-cell specification and plasticity. Methods: We sorted human a- and b-cells and performed the â??Assay for Transposase-Accessible Chromatin with high throughput sequencingâ?? (ATAC-seq) and mRNA-seq, followed by integrative analysis to identify cell type-selective gene regulatory regions. Results: We identified numerous transcripts with either Î±-cell- or Î²-cell-selective expression and discovered the cell type-selective open chromatin regions that correlate with these gene activation patterns. We confirmed cell type-selective expression on the protein level for two of the top hits from our screen. The â??group specific proteinâ?? (GC; or vitamin D binding protein) was restricted to a-cells, while CHODL (chondrolectin) immunoreactivity was only present in b-cells. Furthermore, Î±-cell- and Î²-cell-selective ATAC-seq peaks were identified to overlap with known binding sites for islet transcription factors, as well as with common single nucleotide polymorphisms (SNPs) previously identified as risk loci for type 2 diabetes. Conclusions: We have determined the genetic landscape of human Î±- and Î²-cells based on chromatin accessibility and transcript levels, which allowed for detection of novel Î±- and Î²-cell signature genes not previously known to be expressed in islets. Using fine-mapping of open chromatin, we have identified thousands of potential cis-regulatory elements that operate in an endocrine cell type-specific fashion. ATAC-seq on 3 human alpha cell samples, 3 human beta cell samples, and 2 human acinar cell samples. RNA-seq on 7 human alpha cell samples and 8 human beta cell samples.

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ATAC-seq of a K562 cell line model with a patient-based t(3;8) translocation

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