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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 08, 2024 |
| Title |
A DGCR8/FLII-dominated on-off switch for immediate-early genes governs embryo implantation in mouse and human [Cut&Tag] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
As an essential checkpoint for successful pregnancy, mammalian embryo implantation initiates fetal-maternal communication. However, the underlying transcriptional regulation governing such a fast transition is still unknown. Here, we identify a DGCR8/FLII-dominated on-off switch for immediate-early genes (IEGs) governing pluripotency transition and morphogenesis of epiblasts upon embryo implantation. In mouse naïve embryonic stem cells (mESCs), we find the Microprocessor component DGCR8, but not DROSHA, can recognize mRNA stem-loop structures and further interact with and occupy transcriptional activator FLII to directly suppress transcription of non-miRNA target genes. Interestingly, when mESCs exit from naïve pluripotency, ERK signaling is quickly activated to induce FLII phosphorylation and disrupt DGCR8/FLII interaction. Phosphorylated FLII then binds to AP1, a typical IEG, to mediate the transcriptional activation of cell migration-related genes to establish poised pluripotency. Re-occupation of FLII by DGCR8 drives poised ESCs into formative pluripotency. Disruption of the DGCR8/FLII-mediated transcriptional activation inhibits the naïve-poised-formative ESC transition and the corresponding embryonic morphogenesis during implanting period, which is conserved in mouse and human.
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| Overall design |
To investigate the role of FLII/AP1/DGCR8 in FLII/JUN-mediated gene activation, we performed cut&tag assay of JUN/RNAPII/H3K27ac in different cells including FLII knockout or FLII/JUN overexpression cells during naïve-poised transition and DF-dKO naïve mESC with coexpression of FLII phosphorylation mutants and DGCR8.
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| Contributor(s) |
Lyu X |
| Citation(s) |
38955180 |
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| Submission date |
Feb 20, 2024 |
| Last update date |
Jul 09, 2024 |
| Contact name |
Xuehui Lv |
| E-mail(s) |
lvxuehui0118@pku.edu.cn
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| Organization name |
Peking University
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| Street address |
No.5 Yiheyuan Road, Haidian district, Beijing, 100871, China
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| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (72)
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| GSM8087170 |
RNAPII Cut&Tag, WT mESCs (EpiLC-0h), Rep1 |
| GSM8087171 |
RNAPII Cut&Tag, WT mESCs (EpiLC-1h), Rep1 |
| GSM8087172 |
RNAPII Cut&Tag, WT mESCs (EpiLC-6h), Rep1 |
| GSM8087173 |
RNAPII Cut&Tag, Flii-/- mESCs (EpiLC-0h), Rep1 |
| GSM8087174 |
RNAPII Cut&Tag, Flii-/- mESCs (EpiLC-1h), Rep1 |
| GSM8087175 |
RNAPII Cut&Tag, Flii-/- mESCs (EpiLC-6h), Rep1 |
| GSM8087176 |
RNAPII Cut&Tag, WT mESCs (EpiLC-0h), Rep2 |
| GSM8087177 |
RNAPII Cut&Tag, WT mESCs (EpiLC-1h), Rep2 |
| GSM8087178 |
RNAPII Cut&Tag, WT mESCs (EpiLC-6h), Rep2 |
| GSM8087179 |
RNAPII Cut&Tag, Flii-/- mESCs (EpiLC-0h), Rep2 |
| GSM8087180 |
RNAPII Cut&Tag, Flii-/- mESCs (EpiLC-1h), Rep2 |
| GSM8087181 |
RNAPII Cut&Tag, Flii-/- mESCs (EpiLC-6h), Rep2 |
| GSM8087182 |
H3K27ac Cut&Tag, WT mESCs (EpiLC-0h), Rep1 |
| GSM8087183 |
H3K27ac Cut&Tag, WT mESCs (EpiLC-1h), Rep1 |
| GSM8087184 |
H3K27ac Cut&Tag, WT mESCs (EpiLC-6h), Rep1 |
| GSM8087185 |
H3K27ac Cut&Tag, Flii-/- mESCs (EpiLC-0h), Rep1 |
| GSM8087186 |
H3K27ac Cut&Tag, Flii-/- mESCs (EpiLC-1h), Rep1 |
| GSM8087187 |
H3K27ac Cut&Tag, Flii-/- mESCs (EpiLC-6h), Rep1 |
| GSM8087188 |
H3K27ac Cut&Tag, WT mESCs (EpiLC-0h), Rep2 |
| GSM8087189 |
H3K27ac Cut&Tag, WT mESCs (EpiLC-1h), Rep2 |
| GSM8087190 |
H3K27ac Cut&Tag, WT mESCs (EpiLC-6h), Rep2 |
| GSM8087191 |
H3K27ac Cut&Tag, Flii-/- mESCs (EpiLC-0h), Rep2 |
| GSM8087192 |
H3K27ac Cut&Tag, Flii-/- mESCs (EpiLC-1h), Rep2 |
| GSM8087193 |
H3K27ac Cut&Tag, Flii-/- mESCs (EpiLC-6h), Rep2 |
| GSM8087194 |
JUN Cut&Tag, WT mESCs (EpiLC-0h), Rep1 |
| GSM8087195 |
JUN Cut&Tag, WT mESCs (EpiLC-1h), Rep1 |
| GSM8087196 |
JUN Cut&Tag, WT mESCs (EpiLC-6h), Rep1 |
| GSM8087197 |
JUN Cut&Tag, Flii-/- mESCs (EpiLC-0h), Rep1 |
| GSM8087198 |
JUN Cut&Tag, Flii-/- mESCs (EpiLC-1h), Rep1 |
| GSM8087199 |
JUN Cut&Tag, Flii-/- mESCs (EpiLC-6h), Rep1 |
| GSM8087200 |
JUN Cut&Tag, WT mESCs (EpiLC-0h), Rep2 |
| GSM8087201 |
JUN Cut&Tag, WT mESCs (EpiLC-1h), Rep2 |
| GSM8087202 |
JUN Cut&Tag, WT mESCs (EpiLC-6h), Rep2 |
| GSM8087203 |
JUN Cut&Tag, Flii-/- mESCs (EpiLC-0h), Rep2 |
| GSM8087204 |
JUN Cut&Tag, Flii-/- mESCs (EpiLC-1h), Rep2 |
| GSM8087205 |
JUN Cut&Tag, Flii-/- mESCs (EpiLC-6h), Rep2 |
| GSM8087206 |
JUN Cut&Tag, KH2-FLII (EpiLC-0h, no Dox), Rep1 |
| GSM8087207 |
JUN Cut&Tag, KH2-FLII (EpiLC-0h, + Dox), Rep1 |
| GSM8087208 |
JUN Cut&Tag, KH2-FLII (EpiLC-6h, no Dox), Rep1 |
| GSM8087209 |
JUN Cut&Tag, KH2-FLII (EpiLC-6h, + Dox), Rep1 |
| GSM8087210 |
JUN Cut&Tag, KH2-FLII (EpiLC-0h, no Dox), Rep2 |
| GSM8087211 |
JUN Cut&Tag, KH2-FLII (EpiLC-0h, + Dox), Rep2 |
| GSM8087212 |
JUN Cut&Tag, KH2-FLII (EpiLC-6h, no Dox), Rep2 |
| GSM8087213 |
JUN Cut&Tag, KH2-FLII (EpiLC-6h, + Dox), Rep2 |
| GSM8087214 |
JUN Cut&Tag, KH2JUN (2iLif, no Dox), Rep1 |
| GSM8087215 |
JUN Cut&Tag, KH2JUN (2iLif, + Dox 4h), Rep1 |
| GSM8087216 |
JUN Cut&Tag, KH2JUN (2iLif, + Dox 12h), Rep1 |
| GSM8087217 |
JUN Cut&Tag, KH2JUN (2iLif, no Dox), Rep2 |
| GSM8087218 |
JUN Cut&Tag, KH2JUN (2iLif, + Dox 4h), Rep2 |
| GSM8087219 |
JUN Cut&Tag, KH2JUN (2iLif, + Dox 12h), Rep2 |
| GSM8087220 |
JUN Cut&Tag, WT mESCs (EpiLC-0h), control of the JUN rescue assay. |
| GSM8087221 |
JUN Cut&Tag, Jun-/-Flii-/- mESCs (EpiLC-0h) in which JUN was rescued |
| GSM8087222 |
JUN Cut&Tag, WT mESCs (EpiLC-6h), control of the JUN rescue assay, Rep1 |
| GSM8087223 |
JUN Cut&Tag, Jun-/-Flii-/- mESCs (EpiLC-6h) in which JUN was rescued, Rep1 |
| GSM8087224 |
JUN Cut&Tag, WT mESCs (EpiLC-6h), control of the JUN rescue assay, Rep2 |
| GSM8087225 |
JUN Cut&Tag, Jun-/-Flii-/- mESCs (EpiLC-6h) in which JUN was rescued, Rep2 |
| GSM8087226 |
JUN Cut&Tag, WT mESCs (Serum/Lif medium) |
| GSM8087227 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium), Rep1 |
| GSM8087228 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which WT-FLII was rescued, Rep1 |
| GSM8087229 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which both WT-FLII and DGCR8 were rescued, Rep1 |
| GSM8087230 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which 2D-FLII was rescued, Rep1 |
| GSM8087231 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which both 2D-FLII and DGCR8 were rescued, Rep1 |
| GSM8087232 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which 2A-FLII was rescued, Rep1 |
| GSM8087233 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which both 2A-FLII and DGCR8 were rescued, Rep1 |
| GSM8087234 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium), Rep2 |
| GSM8087235 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which WT-FLII was rescued, Rep2 |
| GSM8087236 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which both WT-FLII and DGCR8 were rescued, Rep2 |
| GSM8087237 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which 2D-FLII was rescued, Rep2 |
| GSM8087238 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which both 2D-FLII and DGCR8 were rescued, Rep2 |
| GSM8087239 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which 2A-FLII was rescued, Rep2 |
| GSM8087240 |
JUN Cut&Tag, DF-dKO mESCs (Serum/Lif medium) in which both 2A-FLII and DGCR8 were rescued, Rep2 |
| GSM8184298 |
JUN Cut&Tag, WT mESCs (EpiLC-0h), in which JUN was rescued |
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| Relations |
| BioProject |
PRJNA1078383 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE256183_RAW.tar |
9.0 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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