Cell type-specific Chromatin Accessibility Analysis in the Mouse and Human Brain (Mouse ATAC-seq experiments)
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ABSTRACT:
PROVIDER: PRJNA645059 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12182284_1.fastq.gz | Fastqsanger.gz | |||
| SRR12182284_2.fastq.gz | Fastqsanger.gz | |||
| SRR12182285_1.fastq.gz | Fastqsanger.gz | |||
| SRR12182285_2.fastq.gz | Fastqsanger.gz | |||
| SRR12182286_1.fastq.gz | Fastqsanger.gz |
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Project description:The Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) is becoming increasing popular in the neuroscience field where chromatin regulation is thought to be involved in neurodevelopment, activity-dependent gene regulation, hormonal and environmental responses, and pathophysiology of neuropsychiatric disorders. The advantages of using this assay include a small amount of material needed, relatively simple and fast protocol, and the ability to capture a range of gene regulatory elements with a single assay. However, with increasing interest in chromatin research, it is an imperative to have feasible, reliable assays that are compatible with a range of neuroscience study designs in both animals and humans. Here we tested three different protocols for neuronal chromatin accessibility analysis, including a varying brain tissue freezing method followed by fluorescent-activated nuclei sorting (FANS) and the ATAC-seq analysis. Our study shows that the cryopreservation method impacts the number of open chromatin regions that can be identified from frozen brain tissue using the cell-type specific ATAC-seq assay. However, we show that all three protocols generate consistent and robust data and enable the identification of functional regulatory elements, promoters and enhancers, in neuronal cells. Our study also implies that the broad biological interpretation of chromatin accessibility data is not significantly affected by the freezing condition. In comparison to the mouse brain analysis, we reveal the additional challenges of doing chromatin analysis on postmortem human brain tissue. However, we also show that these studies are revealing important cell type-specific information about gene regulation in the human brain. Overall, the ATAC-seq coupled with FANS is a powerful method to capture cell-type specific chromatin accessibility information in the mouse and human brain. Our study provides alternative brain preservation methods that generate high quality ATAC-seq data while fitting in different study designs, and further encourages the use of this method to uncover the role of epigenetic (dys)regulation in healthy and malfunctioning brain.
2021-03-10 | GSE154067 | GEO
Project description:Cell type-specific Chromatin Accessibility Analysis in the Mouse and Human Brain (Human ATAC-seq experiments)
| PRJNA645058 | ENA
Project description:The Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) is becoming increasing popular in the neuroscience field where chromatin regulation is thought to be involved in neurodevelopment, activity-dependent gene regulation, hormonal and environmental responses, and pathophysiology of neuropsychiatric disorders. The advantages of using this assay include a small amount of material needed, relatively simple and fast protocol, and the ability to capture a range of gene regulatory elements with a single assay. However, with increasing interest in chromatin research, it is an imperative to have feasible, reliable assays that are compatible with a range of neuroscience study designs in both animals and humans. Here we tested three different protocols for neuronal chromatin accessibility analysis, including a varying brain tissue freezing method followed by fluorescent-activated nuclei sorting (FANS) and the ATAC-seq analysis. Our study shows that the cryopreservation method impacts the number of open chromatin regions that can be identified from frozen brain tissue using the cell-type specific ATAC-seq assay. However, we show that all three protocols generate consistent and robust data and enable the identification of functional regulatory elements, promoters and enhancers, in neuronal cells. Our study also implies that the broad biological interpretation of chromatin accessibility data is not significantly affected by the freezing condition. In comparison to the mouse brain analysis, we reveal the additional challenges of doing chromatin analysis on postmortem human brain tissue. However, we also show that these studies are revealing important cell type-specific information about gene regulation in the human brain. Overall, the ATAC-seq coupled with FANS is a powerful method to capture cell-type specific chromatin accessibility information in the mouse and human brain. Our study provides alternative brain preservation methods that generate high quality ATAC-seq data while fitting in different study designs, and further encourages the use of this method to uncover the role of epigenetic (dys)regulation in healthy and malfunctioning brain.
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Project description:The majority of common genetic risk variants associated with neuropsychiatric disease are non-coding and are thought to exert their effects by disrupting the function of cis regulatory elements (CREs), including promoters and enhancers. Within each cell, chromatin is arranged in specific patterns to expose the repertoire of CREs required for optimal spatiotemporal regulation of gene expression. To further our understanding of the complex mechanisms that modulate transcription in the brain, we utilized frozen postmortem samples to generate the largest human brain and cell type-specific open chromatin dataset to date. Using the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq), we created maps of chromatin accessibility in 2 cell types (neurons and non-neurons) across 14 distinct brain regions of 5 individuals. Chromatin structure varies markedly by cell type, with neuronal chromatin displaying higher regional variability than that of non-neurons. Among our findings is an open chromatin region (OCR) specific to neurons of the striatum. When placed in the mouse, a human sequence derived from this OCR recapitulates the cell-type and regional expression pattern predicted by our ATAC-seq experiments. Furthermore, differentially accessible chromatin overlaps with the genetic architecture of neuropsychiatric traits and identifies differences in molecular pathways and biological functions. By leveraging transcription factor binding analysis, we identify protein coding and long noncoding RNAs (lncRNAs) with cell-type and brain region specificity. Our data provides a valuable resource to the research community and we provide this human brain chromatin accessibility atlas as an online database “Brain Open Chromatin Atlas (BOCA)” to facilitate interpretation.
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Project description:We present FFPE-ATAC, a new ATAC-seq tool for chromatin accessibility profiling that decodes the chromatin accessibility from mouse FFPE tissue and clinical archived FFPE tissues. The FFPE-ATAC generates the high-quality chromatin accessibility profiles from clinical FFPE tissue sections with 5-20 µm thickness, and reveals the disease-associated regulatory elements in different types of FFPE archived tissue. FFPE-ATAC enables to decode the chromatin states regulating the gene regulation in the cancer and understand the epigenetic regulation in the translational studies.
2021-06-30 | GSE163306 | GEO
Project description:Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated through examination of the chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1482 distinct brain cell populations, adding over 446,000 new cCREs to the most recent such annotation in the mouse genome. Raw fastq files are demultiplexed. Out of 234 samples, fastq files for 6 samples are available in NCBI under the accession number GSE126724 (CEMBA180308_3B, CEMBA180312_3B, CEMBA180226_1A, CEMBA180227_1A, CEMBA180305_2B, CEMBA180306_2B). Processed data are SnapATAC2 (<= 2.4.0) h5ad files per sample, with raw fragments and 500-bp bmat. NOTE: due to the break changes in SnapATAC2 >= 2.5.0, the data can not be handled rightly in SnapATAC2 >= 2.5.0.
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Project description:We performed profiling of allele-specific chromatin accessibility profiling in mouse spermatocytes. To this end, we isolated tetraploid spermatocytes using FACS-sorting from F1 crosses of the C57B6J and CAST/EiJ strains. We then performed ATAC-Seq (Corces et al. 2017) and analyzed allele-specific chromatin accessibility.
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