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SRX18912252: GSM6913984: ATAC-seq-WT_Rep2-2iLd3; Mus musculus; ATAC-seq
1 ILLUMINA (Illumina HiSeq 2500) run: 25.6M spots, 2.6G bases, 825.7Mb downloads

External Id: GSM6913984_r1
Submitted by: patrick G Johnston Centre for Cancer research, Queen's University Belfast
Study: (ATAC-seq_and_ChIP-seq) Spic regulates one-carbon metabolism and histone methylation in ground-state pluripotency
show Abstracthide Abstract
Understanding mechanisms of epigenetic regulation in embryonic stem cells (ESCs) is of fundamental importance for stem cell and developmental biology. Here we identify Spic, a member of the ETS family of transcription factors, as a specific marker of ground state pluripotency. We show that Spic is rapidly induced in ESCs cultured with GSK3-, MEK-inhibitors and LIF (2iL), and in response to MEK/ERK inhibition. ChIP-seq analysis demonstrated that Spic binds to enhancer elements that are associated with pluripotency genes. Interaction proteomics and genomic profiling confirmed that SPIC interacts with NANOG and stabilizes its binding to chromatin in 2iL-ESCs. Additional gain of function and loss of function experiments revealed that Spic controls genes involved in one carbon (1C) metabolism, Bhmt, Bhmt2, and Dmgdh, and the flux of SAM-to-SAH in 2iL-ESCs. By maintaining low levels of SAM, Spic controls the level of H3K4me3 and H3R17me2 histone methylation in ground state ESCs. Our data highlight the role of uncharacterized axillary transcription factors that link cellular metabolism to epigenetic regulation in ground state pluripotency. Overall design: ATAC-seq and ChIP-seq of SPIC and NANOG in Spic-KO, -OE, and -WT mouse ESCs
Sample: ATAC-seq-WT_Rep2-2iLd3
SAMN32541675 • SRS16340083 • All experiments • All runs
Organism: Mus musculus
Library:
Name: GSM6913984
Instrument: Illumina HiSeq 2500
Strategy: ATAC-seq
Source: GENOMIC
Selection: other
Layout: PAIRED
Construction protocol: mESCs were cultured in SL or 2iL medium for 3 days. For each replicate, 15 million cells were fixed with 1% paraformaldehyde. Fixed cells were consecutively treated with buffers A (148mM NaCl, 1.48 mM EDTA, 0.74 mM EGTA, 74mM HEPES), Buffer-B (10 mM EDTA, 0.5 mM EGTA, 20 mM HEPES, 0.25% Triton-x100), and Buffer-C (150 mM NaCl, 1 mM EDTA, 0.5 mM EGTA, 50 mM HEPES). Isolated nuclei were lysed in freshly made sonication buffer (150 mM NaCl, 1 mM EDTA, 0.5 mM EGTA, 20 mM HEPES, 0.15% SDS, 1% TritonX-100, 1X protease inhibitor) and samples were sonicated using Biorapture Pico (Diagenode). Sonicated chromatin was precleared using BSA blocked protein A/G beads (Invitrogen), and was further incubated with 10 µg of primary antibody (anti-FLAG from Sigma for NANOG ChIP, and anti-GFP from Abcam for SPIC-GFP ChIP). After overnight incubation, the immune complexes were captured by incubation with BSA blocked protein A/G beads for 2h on a rotating wheel at 4ºC. Beads were washed with ChIP wash buffer 1 (2 mM EDTA, 20 mM Tris pH:8 150 mM NaCl, 1% TritonX-100, 0.1% SDS), Buffer-2 (2 mM EDTA, 20 mM Tris pH:8 150 mM NaCl, 1% TritonX-100, 0.1% SDS, 500 mM NaCl) and Buffer-3 (1 mM EDTA, 10 mM Tris pH:8) for 10 minutes. Samples were then incubated with fresh ChIP elution buffer (0.1 M NaHCO3, 1% SDS) for 30 min at RT. Eluted chromatin was de-crosslinked overnight by adding 5M NaCl and proteinase K (final 10mg/ml) and incubating at 65ºC. DNA was purified using the MinElute PCR Purification Kit (Qiagen) ChIP-Rx-seq libraries were subjected to library preparation using the KAPA HyperPrep kit (Roche) according to manufacturer's instructions with dual indices and sequencing on an Illumina HiSeq 2500 sequencer (dual-indexed 50-bp paired-end reads).
Runs: 1 run, 25.6M spots, 2.6G bases, 825.7Mb
Run# of Spots# of BasesSizePublished
SRR2295533525,602,0632.6G825.7Mb2023-09-06

ID:
26023051

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