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SRX18988637: GSM6925414: LSD1_HCT116_KO_H3K4me1_rep2; Homo sapiens; ChIP-Seq
1 ILLUMINA (Illumina HiSeq 2500) run: 38.9M spots, 11.7G bases, 3.5Gb downloads

External Id: GSM6925414_r1
Submitted by: School of Medicine, Sun Yat-sen University
Study: Pan-cancer analysis revealed H3K4me1 at bivalent promoters premarks DNA hypermethylation during tumor development and identified the regulatory role of DNA methylation in relation to histone modifications [ChIP-seq]
show Abstracthide Abstract
Background: DNA hypermethylation at promoter CpG islands (CGIs) is a hallmark of cancers and could lead to dysregulation of gene expression in the development of cancers, however, its dynamics and regulatory mechanisms remain elusive. Bivalent genes, that direct development and differentiation of stem cells, are found to be frequent targets of hypermethylation in cancers. Results: Here we performed comprehensive analysis across multiple cancer types and identified that the decrease in H3K4me1 levels coincides with DNA hypermethylation at the bivalent promoter CGIs during tumorigenesis. Removal of DNA hypermethylation leads to increment of H3K4me1 at promoter CGIs with preference for bivalent genes. Nevertheless, the alteration of H3K4me1 by overexpressing or knockout LSD1, the demethylase of H3K4, doesn't change the level or pattern of DNA methylation. Moreover, LSD1 was found to regulate the expression of a bivalent gene OVOL2 to promote tumorigenesis. Knockdown of OVOL2 in LSD1 knockout HCT116 cells restored the cancer cell phenotype. Conclusion: In summary, our work identified a universal indicator that can pre-mark DNA hypermethylation in cancer cells, and dissected the interplay between H3K4me1 and DNA hypermethylation in detail. Current study also reveals a novel mechanism underlying the oncogenic role of LSD1, providing clues for cancer therapies. Overall design: we performed comprehensive analysis across multiple cancer types and identified that DNA hypermethylation in cancers can be predicated by enriched unimodal pattern of Histone H3 lysine 4 mono-methylation (H3K4me1) in corresponding normal tissues.
Sample: LSD1_HCT116_KO_H3K4me1_rep2
SAMN32658657 • SRS16409216 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM6925414
Instrument: Illumina HiSeq 2500
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: 5x 106 cells were cross-linked with 1% formaldehyde for 10 minutes and quenched by 125mM glycine for 5 minutes at room temperature with gentle shaking, and washed twice with PBS. Cells were then pelleted and lysed in ice-cold lysis buffer1 (50mM HEPES-KOH, pH 7.5, 140mM NaCl, 1mM EDTA, 10% Glycerol, 0.5% NP-40, 0.25% Triton X-100) and lysis buffer 2 (10mM Tris-HCl pH 8.0, 200mM NaCl, 1mM EDTA, 0.5mM EGTA) supplemented with cOmplete protease inhibitors (Roche) for 10 minutes. The cell lysate was sonicated using Covaris M220 with 5% duty factor for 10min at 4 °C to shear DNA to fragments (200~1000 bp). Soluble chromatin was diluted in shearing buffer (1mM EDTA, 10mM Tris-HCl pH 8.0, 0.1% SDS) with 1% Triton X-100 and 150 mM NaCl and incubated with 3μg ChIP-grade antibody at 4°C overnight with gentle shaking. 5% of input was stored prior to the de-crosslinking procedure. 30μl Protein-G magnetic beads (Thermo Fisher Scientific, 01134323) was used for subsequent pull-down of antibody-chromatin complex by incubatioin for 2 hours at 4°C with gentle shaking. The beads were washed with following buffers for 2 times each: IP buffer (0.1% SDS, 1% Triton X-100, 1mM EDTA, 150mM NaCl, 10mM Tris-HCl pH 8.0), High Salt Wash Buffer (0.1% SDS, 1% Triton X-100, 2mM EDTA, 500mM NaCl, 20mM Tris-HCl pH 8.0), LiCl Wash Buffer (250mM LiCl, 1% NP-40, 2mM EDTA, 10mM Tris-HCl pH 8.0), and TE buffer+50mM NaCl (1mM EDTA, 50mM NaCl, 10mM Tris-HCl pH 8.0) 1 times. DNA was eluted with Elution Buffer (1% SDS, 10mM EDTA, 50mM Tris-HCl pH 8.0) at 65℃ for 30 minutes with shaking at 1,400 rpm. The supernatant was then collected and incubated at 65°C for overnight to reverse-crosslink the DNA. The day after, the enriched DNA was treated with 4 µL of 20 mg/mL RNase at 37 °C for 2 h and 4 µL of 20 mg/mL Proteinase K (MIKX, FZ690) at 55°C for 2h. The immunoprecipitation DNA was purified by phenol-chloroform-isoamyl alcohol (Solarbio, P1012-100), washed with ethanol, eluted in nuclease-free water, and used for subsequent experiments. The following antibodies were used in ChIP: H3K4me1 (Abcam, ab8895), H3K4me3 (Abcam, ab8580) Sequencing libraries were constructed and sequenced by the Novogene Bioinformatics Institute (Novogene, Beijing, China).
Runs: 1 run, 38.9M spots, 11.7G bases, 3.5Gb
Run# of Spots# of BasesSizePublished
SRR2303397538,876,06511.7G3.5Gb2023-01-12

ID:
26137124

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