Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation

Abstract

T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells. Using a well-established ex vivo protocol of canonical T-cell receptor signaling, we generated genome-wide chromatin maps of naïve T-cells from pediatric donors in quiescent or recently activated states. We identified thousands of individual chromatin accessibility peaks that are associated with T-cell activation, the majority of which were annotated intronic and intergenic enhancer regions. A core set of 3268 gene promoters underwent chromatin remodeling and concomitant changes in gene expression in response to activation, and were enriched in multiple pathways controlling cell cycle regulation, metabolism, inflammatory response genes and cell survival. Leukemia inhibitory factor (LIF) was among those factors that gained the highest accessibility and expression, in addition to IL2-STAT5 dependent chromatin remodeling in the T-cell activation response. Using publicly available data we found the chromatin response was far more dynamic at 24-h compared with 72-h post-activation. In total 546 associations were reproduced at both time-points with similar strength of evidence and directionality of effect. At the pathways level, the IL2-STAT5, KRAS signalling and UV response pathways were replicable at both time-points, although differentially modulated from 24 to 72 h post-activation.

The Landscape of Accessible Chromatin during Yak Adipocyte Differentiation

“…Meanwhile, increasing evidence suggests that enhancer–promoter interactions are also crucial for gene expression regulation [ 31 ]. Studies have shown that the majority of chromatin accessibility found during induction of T cell activation by omni ATAC-seq were located in intergenic enhancer regions [ 32 ]. A large fraction of chromatin accessibility in our study was located in intergenic regions, further suggesting that enhancers may interact with TFs and promoters to regulate gene expression during yak adipocyte differentiation.…”

Immuno‐epigenomic analysis identifies attenuated interferon responses in naïve CD4 T cells of adolescents with peanut and multi‐food allergy

“…To determine the likelihood that changes in DNA methylation corresponded to changes in chromatin accessibility, we compared these activation‐associated DMPs (commonly activated, NA‐specific and FA‐specific) with a publicly available ATAC‐seq dataset for nCD4T cells at quiescence and following activation using the same approach (72 h with anti‐CD3/CD28) 34 . We identified enrichment for ATAC‐peaks in commonly activated DMPs (33% relative to 21% for all EPIC probes; [ Χ 2 (3, N = 11,584) = 82.7, p value <.01)] (Figure S2).…”

“…Assay for Transposable Accessible Chromatin (ATAC)‐seq fastq files for quiescent and activated T cells were downloaded from GEO (GSE157174) 34 . ATAC‐seq reads were aligned to human genome assembly hg19 using bwa 35 .…”

“…Assay for Transposable Accessible Chromatin (ATAC)-seq fastq files for quiescent and activated T cells were downloaded from GEO (GSE157174). 34 ATAC-seq reads were aligned to human genome assembly hg19 using bwa. 35 BAM files were first filtered to remove the reads with mapping quality <15 using samtools, 36 and MACS2…”

Cohesin-Mediated Chromatin Interactions and Autoimmunity

“…Activated and differentiated T-helper cells possessed differentially expressed accessible chromatin region at enhancers and introns compared to quiescent counterparts ( 84 ). This indicates a rapid remodelling of the genome under stimulation.…”