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| Status |
Public on Apr 04, 2020 |
| Title |
GR and LSD1/KDM1A-targeted gene activation requires selective H3K4me2 demethylation at enhancers |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
KDM1A-mediated H3K4 demethylation is a well-established mechanism underlying transcriptional gene repression, but its role in gene activation is less clear. Here we report a critical function and novel mechanism of action of KDM1A in glucocorticoid receptor (GR)-mediated gene transcription. Biochemical purification of the nuclear GR complex revealed KDM1A as an integral component. In cell-free assays, GR modulates KDM1A-catalyzed H3K4 progressive demethylation by limiting loss of H3K4me1. Similarly, in cells KDM1A binds to most GR binding sites where it removes preprogrammed H3K4me2 but leaves H3K4me1 untouched. Blocking KDM1A catalytic activity prevents H3K4me2 removal, severely impairs GR binding to chromatin, and dysregulates GR-targeted genes. Taken together, these data suggest KDM1A-mediated H3K4me2 demethylation at GRBSs promotes GR binding and plays an important role in glucocorticoid-induced gene transcription, offering a new mechanism contributing to nuclear receptor mediated gene activation.
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| Overall design |
ChIP-Seq dataset: A549 cell ChIP-seq under treatment with ethanol (vehicle), dexamethasone, or tranylcypromine (TCP). ChIP against GR, KDM1A, H3K4me1,2,3, H3K9me1,2, and H3K27ac.
RNA-Seq dataset: A549 cell RNA-seq under treatment with ethanol (vehicle), dexamethasone.
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| Contributor(s) |
Shi Y, Clark E, Wu F, Fang R |
| Citation(s) |
31216473 |
| Submission date |
Dec 27, 2017 |
| Last update date |
Apr 04, 2020 |
| Contact name |
Feizhen Wu |
| E-mail(s) |
wufz@fudan.edu.cn
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| Phone |
86-21-54237821
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| Organization name |
Fudan Univ, Shanghai, China
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| Department |
Institutes of Biomedical Sciences
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| Lab |
Epigenetics lab
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| Street address |
Dongan Road 131, Rm 511 Mingdao Building
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| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (2) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA427724 |
| SRA |
SRP127633 |
| SRA |
SRP201035 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108588_DEseq2_results_and_TSS_annotation.csv.gz |
1.9 Mb |
(ftp)(http) |
CSV |
| GSE108588_RAW.tar |
4.1 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
| GSE108588_mean_counts_and_stdev.csv.gz |
488.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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