U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX18393591: GSM6757716: gd7, 1.5to2, atac, 1; Drosophila melanogaster; ATAC-seq
1 ILLUMINA (NextSeq 500) run: 60.5M spots, 9.2G bases, 3.2Gb downloads

External Id: GSM6757716_r1
Submitted by: Zeitlinger, Stowers Institute for Medical Research
Study: Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [ATAC-seq]
show Abstracthide Abstract
Spatiotemporal gene regulation during embryonic development is driven by cis-regulatory DNA sequences called enhancers. Enhancers are activated through a combination of transcription factors (TFs) that bind to short sequence motifs within these sequences, but the order of events by which TFs read out motifs is not clear. Some TFs can only bind chromatin that is already accessible, while other TFs called pioneers can open chromatin themselves. Identifying motifs and the order by which they drive chromatin accessibility is very challenging. The recent implementation of convolutional neural networks, which learn complex cis-regulatory sequence rules that are predictive for genomics data, provides an unprecedented opportunity to dissect this problem. Here, we trained base-resolution deep learning models and applied them to high-resolution TF binding and chromatin accessibility data from the well-studied early Drosophila embryo. We uncover a clear hierarchical relationship between the pioneer Zelda and the TFs involved in the spatiotemporal patterning of the embryo, consistent with Zelda being a pioneer. However, the models predict that patterning TFs can also augment chromatin accessibility in a context-specific manner. Using a series of Drosophila mutant strains, we find that the two types of TFs increase chromatin accessibility by distinct mechanisms. Zelda's pioneering is proportional to motif affinity, while the patterning TFs specifically increase chromatin accessibility when they mediate enhancer activation. This was conclusive because Dorsal can function both as activator and repressor, and the effect on chromatin accessibility depended on Dorsal's transactivation effect and not on its binding per se. In conclusion, chromatin accessibility occurs in two phases: one through pioneering, which makes regions first accessible but not necessarily active, and a second when the correct combination of transcription factors lead to enhancer activation. Overall design: Assay for transposase-accessible chromatin DNA-sequencing (ATAC-seq) in wt Drosophila melanogaster embryos, zld- mutant embryos, gd7 mutant embryos, and cic6 mutant embryos. ATAC-seq experiments were done in a time course manner in 30 minute windows spanning the maternal-to-zygotic transition.
Sample: gd7, 1.5to2, atac, 1
SAMN31886406 • SRS15877704 • All experiments • All runs
Library:
Name: GSM6757716
Instrument: NextSeq 500
Strategy: ATAC-seq
Source: GENOMIC
Selection: other
Layout: PAIRED
Construction protocol: For ATAC-seq time course experiments, the following amounts of hand-sorted embryos were used: 400 embryos (1-1.5 h AEL); 100 embryos (1.5-2 h AEL); 40 embryos (2-2.5 h AEL, 2.5-3 h AEL). Following sorting, embryos were immediately dounced in ATAC Resuspension Buffer (10 mM Tris-HCl pH 7.4, 10 mM NaCl, 3 mM MgCl2) with 0.1% IGEPAL CA-630 and nuclei were harvested by centrifugation. The nuclear pellet was incubated for 3 minutes on ice in ATAC resuspension buffer supplemented with 0.1% IGEPAL CA-630, 0.1% Tween-20, and 0.01% Digitonin (Promega, G9441). The reaction was stopped by adding ATAC Resuspension Buffer with 0.1% Tween-20 followed by centrifugation. Tagmentation took place at 37°C for 30 minutes at 1000 rpm in a 50 µL reaction volume containing 10 µL of 5x Tagment DNA Buffer (50 mM Tris-HCl pH 7.4, 25 mM MgCl2, 50% DMF) 16.5 µL 1x PBS, 0.5 µL 10% Tween-20, 0.5 µL 1% Digitonin, 1-2 µM assembled transposome, and water. Accessible fragments were purified using the Monarch PCR & DNA Cleanup Kit (NEB). Libraries were constructed using Illumina Nextera Dual Indexing, and qPCR was used to prevent over-amplification as done in Corces et al., 2017. ATAC-seq for chromatin accessibility using standard Illumina protocols.
Runs: 1 run, 60.5M spots, 9.2G bases, 3.2Gb
Run# of Spots# of BasesSizePublished
SRR2242409760,451,9239.2G3.2Gb2022-12-20

ID:
25416549

Supplemental Content

Search details

See more...

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...