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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 14, 2023 |
| Title |
Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Cancer cells undergo transcriptional reprogramming to drive tumorigenesis and caner progression. Here, we identified the transcriptional complex, NELF (Negative elongation factor), as an important regulator of this process. Using cancer cell lines and patient-derived tumor organoids, we demonstrated that loss of NELF inhibits breast cancer. Specifically, we found that epithelial-mesenchymal transition (EMT) and stemness-associated genes are downregulated in NELF-depleted breast cancer cells. Afterwards, we pinpointed that SLUG, a key EMT transcription factor, was a top hit of NELF interactome during EMT progression. Furthermore, ChIP-seq analysis revealed that loss of NELF led to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identified the histone acetyltransferase, KAT2B, as a key functional target of NELF-E-SLUG. Genetic and pharmacological inactivation of KAT2B ameliorate expression of critical EMT marker genes, phenocopying NELF ablation. Elevated NELF-E and KAT2B expressions are associated with poorer prognosis in breast cancer patients, highlighting the clinical relevance of our findings. Taken together, we uncovered a crucial role of the NELF-E-KAT2B epigenetic axis in breast cancer carcinogenesis.
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| Overall design |
RNA-seq of CRISPR/CAS9-mediated NELF-E KO MCF7, BT549 and SUM159 cell lines and their parental wildtype lines, NELF-E/scrambled shRNA transduced MCF7ras+SS cells and KAT2B/scrambled siRNA transfected MCF7ras+SS cells with the induction of Doxycycline or DMSO vehicle, Doxycycline-induced MCF7ras+SS cells treated with Garcinol (GA) or DMSO vehicle. ChIP-seq of NELF-E, RNAP II, SLUG and KAT2B in corresponding MCF7ras+SS cells.
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| Web link |
https://www-nature-com.ejproxy.a-star.edu.sg/articles/s41467-023-38132-1
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| Contributor(s) |
Zhang J, Hu Z, Tee W |
| Citation(s) |
37117180 |
| |
| Submission date |
Jan 31, 2022 |
| Last update date |
May 09, 2023 |
| Contact name |
Zhenhua hu |
| E-mail(s) |
zhhu@imcb.a-star.edu.sg
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| Phone |
65869644
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| Organization name |
IMCB, A*STAR
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| Street address |
31 Biopolis drive
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| City |
Singapore |
| State/province |
singapore |
| ZIP/Postal code |
138673 |
| Country |
Singapore |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (76)
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| GSM5849768 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, Con_input, rep1 |
| GSM5849769 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, Con_input, rep2 |
| GSM5849770 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, Con_IP, rep1 |
| GSM5849771 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, Con_IP, rep2 |
| GSM5849772 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, DOX_input, rep1 |
| GSM5849773 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, DOX_input, rep2 |
| GSM5849774 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, DOX_IP, rep1 |
| GSM5849775 |
ChIP-seq, MCF7Ras_KAT2B-ChIP, DOX_IP, rep2 |
| GSM5849776 |
ChIP-seq, MCF7Ras_NELFE-ChIP, Con_input, rep1 |
| GSM5849777 |
ChIP-seq, MCF7Ras_NELFE-ChIP, Con_input, rep2 |
| GSM5849778 |
ChIP-seq, MCF7Ras_NELFE-ChIP, Con_IP, rep1 |
| GSM5849779 |
ChIP-seq, MCF7Ras_NELFE-ChIP, Con_IP, rep2 |
| GSM5849780 |
ChIP-seq, MCF7Ras_NELFE-ChIP, DOX_input, rep1 |
| GSM5849782 |
ChIP-seq, MCF7Ras_NELFE-ChIP, DOX_IP, rep1 |
| GSM5849783 |
ChIP-seq, MCF7Ras_NELFE-ChIP, DOX_IP, rep2 |
| GSM5849793 |
ChIP-seq, scramble_DOX_inputFor_NELFErep2_AND_SLUG, rep1 |
| GSM5849794 |
ChIP-seq, scramble_DOX_inputFor_NELFErep2_AND_SLUG, rep2 |
| GSM5849795 |
ChIP-seq, shNELFE_MCF7Ras_SLUG-ChIP, scramble_DOX_IP, rep1 |
| GSM5849796 |
ChIP-seq, shNELFE_MCF7Ras_SLUG-ChIP, scramble_DOX_IP, rep2 |
| GSM5849797 |
ChIP-seq, shNELFE_MCF7Ras_SLUG-ChIP, shNELFE_DOX_input, rep1 |
| GSM5849798 |
ChIP-seq, shNELFE_DOX_inputFor_RNAPII_AND_SLUG, rep2 |
| GSM5849799 |
ChIP-seq, shNELFE_MCF7Ras_SLUG-ChIP, shNELFE_DOX_IP, rep1 |
| GSM5849800 |
ChIP-seq, shNELFE_MCF7Ras_SLUG-ChIP, shNELFE_DOX_IP, rep2 |
| GSM5849801 |
RNA-seq, MCF7, NELFEKO, rep1 |
| GSM5849802 |
RNA-seq, MCF7, NELFEKO, rep2 |
| GSM5849803 |
RNA-seq, MCF7Ras, DMSO_DOX, rep1 |
| GSM5849804 |
RNA-seq, MCF7Ras, DMSO_DOX, rep2 |
| GSM5849805 |
RNA-seq, MCF7Ras, GA_DOX, rep1 |
| GSM5849806 |
RNA-seq, MCF7Ras, GA_DOX, rep2 |
| GSM5849807 |
RNA-seq, MCF7, WT, rep1 |
| GSM5849808 |
RNA-seq, MCF7, WT, rep2 |
| GSM5849809 |
RNA-seq, shNELFE_MCF7Ras, scramble_Con, rep1 |
| GSM5849810 |
RNA-seq, shNELFE_MCF7Ras, scramble_Con, rep2 |
| GSM5849811 |
RNA-seq, shNELFE_MCF7Ras, scramble_DOX, rep1 |
| GSM5849812 |
RNA-seq, shNELFE_MCF7Ras, scramble_DOX, rep2 |
| GSM5849813 |
RNA-seq, shNELFE_MCF7Ras, shNELFE_Con, rep1 |
| GSM5849814 |
RNA-seq, shNELFE_MCF7Ras, shNELFE_Con, rep2 |
| GSM5849815 |
RNA-seq, shNELFE_MCF7Ras, shNELFE_DOX, rep1 |
| GSM5849816 |
RNA-seq, shNELFE_MCF7Ras, shNELFE_DOX, rep2 |
| GSM5849817 |
RNA-seq, siKAT2B_MCF7Ras, scramble_DOX, rep1 |
| GSM5849818 |
RNA-seq, siKAT2B_MCF7Ras, scramble_DOX, rep2 |
| GSM5849819 |
RNA-seq, siKAT2B_MCF7Ras, siKAT2B_DOX, rep1 |
| GSM5849820 |
RNA-seq, siKAT2B_MCF7Ras, siKAT2B_DOX, rep2 |
| GSM5849821 |
RNA-seq, SUM159, NELFEKO, rep1 |
| GSM5849822 |
RNA-seq, SUM159, NELFEKO, rep2 |
| GSM5849823 |
RNA-seq, SUM159, WT, rep1 |
| GSM5849824 |
RNA-seq, SUM159, WT, rep2 |
| GSM7151669 |
ChIP-seq.MCF7Ras_NELFE-ChIP_forGA.DOX_DMSO_input |
| GSM7151670 |
ChIP-seq.MCF7Ras_NELFE-ChIP_forGA.DOX_DMSO_IP_rep1 |
| GSM7151671 |
ChIP-seq.MCF7Ras_NELFE-ChIP_forGA.DOX_DMSO_IP_rep2 |
| GSM7151672 |
ChIP-seq.MCF7Ras_NELFE-ChIP_forGA.DOX_GA_input |
| GSM7151673 |
ChIP-seq.MCF7Ras_NELFE-ChIP_forGA.DOX_GA_IP_rep1 |
| GSM7151674 |
ChIP-seq.MCF7Ras_NELFE-ChIP_forGA.DOX_GA_IP_rep2 |
| GSM7151675 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_Con_input |
| GSM7151676 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_Con_IP_rep1 |
| GSM7151677 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_Con_IP_rep2 |
| GSM7151678 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_DOX_input |
| GSM7151679 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_DOX_IP_rep1 |
| GSM7151680 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_DOX_IP_rep2 |
| GSM7151681 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.shNELFE_DOX_input |
| GSM7151682 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.shNELFE_DOX_IP_rep1 |
| GSM7151683 |
ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.shNELFE_DOX_IP_rep2 |
| GSM7151684 |
ChIP-seq.BT549_NELFE-ChIP.scramble_input_rep1 |
| GSM7151685 |
ChIP-seq.BT549_NELFE-ChIP.scramble_input_rep2 |
| GSM7151686 |
ChIP-seq.BT549_NELFE-ChIP.scramble_IP_rep1 |
| GSM7151687 |
ChIP-seq.BT549_NELFE-ChIP.scramble_IP_rep2 |
| GSM7151688 |
ChIP-seq.BT549_SLUG-ChIP.scramble_input |
| GSM7151689 |
ChIP-seq.BT549_SLUG-ChIP.scramble_IP_rep1 |
| GSM7151690 |
ChIP-seq.BT549_SLUG-ChIP.scramble_IP_rep2 |
| GSM7151691 |
ChIP-seq.BT549_SLUG-ChIP.shNELFE_input |
| GSM7151692 |
ChIP-seq.BT549_SLUG-ChIP.shNELFE_IP_rep1 |
| GSM7151693 |
ChIP-seq.BT549_SLUG-ChIP.shNELFE_IP_rep2 |
| GSM7151694 |
RNA-seq.BT549.shNELFE_rep1 |
| GSM7151695 |
RNA-seq.BT549.shNELFE_rep2 |
| GSM7151696 |
RNA-seq.BT549.WT_rep1 |
| GSM7151697 |
RNA-seq.BT549.WT_rep2 |
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| Relations |
| BioProject |
PRJNA802117 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE195761_ChIP-seq.BT549_SLUG-ChIP.scramble_rep12.bw |
780.3 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.BT549_SLUG-ChIP.shNELFE_rep12.bw |
777.7 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.MCF7Ras_KAT2B-ChIP.Con_rep12.bw |
826.5 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.MCF7Ras_KAT2B-ChIP.DOX_rep12.bw |
828.6 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.MCF7Ras_NELFE-ChIP.Con_rep12.bw |
737.7 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.MCF7Ras_NELFE-ChIP.DOX_DMSO_rep12.bw |
760.9 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.MCF7Ras_NELFE-ChIP.DOX_GA_rep12.bw |
778.2 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.MCF7Ras_NELFE-ChIP.DOX_rep12.bw |
739.8 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_Con_rep12.bw |
802.3 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.scramble_DOX_rep12.bw |
770.1 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.shNELFE_MCF7Ras_RNAPII-ChIP.shNELFE_DOX_rep12.bw |
764.3 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.shNELFE_MCF7Ras_SLUG-ChIP.scramble_DOX_rep12.bw |
760.0 Mb |
(ftp)(http) |
BW |
| GSE195761_ChIP-seq.shNELFE_MCF7Ras_SLUG-ChIP.shNELFE_DOX_rep12.bw |
760.7 Mb |
(ftp)(http) |
BW |
| GSE195761_RAW.tar |
23.3 Mb |
(http)(custom) |
TAR (of RESULTS) |
| GSE195761_RNA-seq.xlsx |
14.6 Mb |
(ftp)(http) |
XLSX |
| GSE195761_peaks_BT549.scramble_NELFE_rep12_np09.bed.gz |
124.3 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_BT549.scramble_SLUG_rep12_np09.bed.gz |
354.6 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_MCF7Ras.Con_KAT2B_rep12_np09.bed.gz |
120.1 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_MCF7Ras.DOX_KAT2B_rep12_np09.bed.gz |
13.9 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_MCF7Ras.scramble_Con_NELFE_rep12_np09.bed.gz |
190.8 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_MCF7Ras.scramble_DOX_NELFE_rep12_np09.bed.gz |
187.3 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_MCF7Ras.scramble_DOX_SLUG_rep12_np09.bed.gz |
225.4 Kb |
(ftp)(http) |
BED |
| GSE195761_peaks_MCF7Ras.shNELFE_DOX_SLUG_rep12_np09.bed.gz |
191.7 Kb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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