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Status |
Public on Jul 08, 2024 |
Title |
Mechanism for controlled assembly of transcriptional condensates by Aire |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Transcriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. We here report a multi-layered mechanism for condensate assembly by Autoimmune regulator (Aire), an essential transcriptional regulator (TR) that orchestrates gene expression reprogramming for central T-cell tolerance. Aire condensates assemble on enhancers, stimulating local transcriptional activities and connecting disparate inter-chromosomal loci. This functional condensate formation hinges upon the coordination between three Aire domains: polymerization domain CARD, histone binding domain PHD1 and C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting Aire to CBP/p300-rich enhancers and promoting CARD-mediated condensate assembly. Conversely, PHD1 binds to the ubiquitous histone mark H3K4me0, keeping Aire dispersed throughout the genome until Aire nucleates on enhancers. Our findings showed that the balance between PHD1-mediated suppression and CTT-mediated stimulation of Aire polymerization is crucial to form transcriptionally active condensates at target sites, providing new insights into controlled polymerization of TRs. This SuperSeries is composed of the SubSeries listed below.
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Overall design |
Refer to individual Series
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Contributor(s) |
Hur S, Huoh Y, Zhang Q |
Citation(s) |
39169234 |
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Submission date |
Sep 22, 2023 |
Last update date |
Sep 30, 2024 |
Contact name |
Qianxia Zhang |
E-mail(s) |
qianxia.zhang@childrens.harvard.edu
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Phone |
9018345955
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Organization name |
Boston Children's Hospital
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Street address |
3 Blackfan Circle, RM 3117.16
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02115 |
Country |
USA |
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Platforms (3) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
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Samples (75)
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GSM7796125 |
WT AIRE 4D6, Dox, rep2 |
GSM7796126 |
Day7_mKate2_Neg_rep1 |
GSM7796127 |
Day7_mKate2_Neg_rep2 |
GSM7796128 |
Day7_mKate2_Neg_rep3 |
GSM7796129 |
Day7_mKate2_Pos_rep1 |
GSM7796130 |
Day7_mKate2_Pos_rep2 |
GSM7796131 |
Day7_mKate2_Pos_rep3 |
GSM7796132 |
Day10_mKate2_Neg_rep1 |
GSM7796133 |
Day10_mKate2_Neg_rep2 |
GSM7796134 |
Day10_mKate2_Neg_rep3 |
GSM7796135 |
Day10_mKate2_Pos_rep1 |
GSM7796136 |
Day10_mKate2_Pos_rep2 |
GSM7796137 |
Day10_mKate2_Pos_rep3 |
GSM7796138 |
AIRE WT, input ctrl |
GSM7796139 |
AIRE WT, ChIP, rep1 |
GSM7796140 |
AIRE WT, ChIP, rep2 |
GSM7796141 |
AIRE DCTT.R3, input ctrl |
GSM7796142 |
AIRE DCTT.R3, ChIP , rep1 |
GSM7796143 |
AIRE DCTT.R3, ChIP , rep2 |
GSM7796144 |
AIRE DCARD, input ctrl |
GSM7796145 |
AIRE DCARD, ChIP, rep1 |
GSM7796146 |
AIRE DCARD, ChIP, rep2 |
GSM7796147 |
AIRE DPHD1, input ctrl |
GSM7796148 |
AIRE DPHD1, ChIP, rep1 |
GSM7796149 |
AIRE DPHD1, ChIP, rep2 |
GSM7796150 |
AIRE WT, DMSO, rep1 |
GSM7796151 |
AIRE WT, DMSO, rep2 |
GSM7796152 |
AIRE WT, DMSO, rep3 |
GSM7796153 |
AIRE WT, dCBP1, rep1 |
GSM7796154 |
AIRE WT, dCBP1, rep2 |
GSM7796155 |
AIRE WT, A485, rep1 |
GSM7796156 |
AIRE WT, A485, rep2 |
GSM7796157 |
AIRE WT, A485, rep3 |
GSM7796158 |
p300, no Dox, rep1 |
GSM7796159 |
p300, no Dox, rep2 |
GSM7796160 |
H3K27ac, no Dox, rep1 |
GSM7796161 |
H3K27ac, no Dox, rep2 |
GSM7796162 |
H3K27ac, no Dox, rep3 |
GSM7796163 |
H3K4me1, no Dox, rep1 |
GSM7796164 |
H3K4me1, no Dox, rep2 |
GSM7796165 |
H3K4me1, no Dox, rep3 |
GSM7796166 |
H3K27me3, no Dox, rep1 |
GSM7796167 |
H3K27me3, no Dox, rep2 |
GSM7796168 |
H3K27me3, no Dox, rep3 |
GSM8268200 |
H3K4me1, Dox, rep1 |
GSM8268201 |
H3K4me1, Dox, rep2 |
GSM8268202 |
H3K4me1, Dox, rep3 |
GSM8268203 |
H3K4me3, no Dox, rep1 |
GSM8268204 |
H3K4me3, no Dox, rep2 |
GSM8268205 |
H3K4me3, no Dox, rep3 |
GSM8268206 |
H3K4me3, Dox, rep1 |
GSM8268207 |
H3K4me3, Dox, rep2 |
GSM8268208 |
H3K4me3, Dox, rep3 |
GSM8268209 |
H3K4me0, no Dox, rep1 |
GSM8268210 |
H3K4me0, no Dox, rep2 |
GSM8268211 |
H3K4me0, no Dox, rep3 |
GSM8268212 |
H3K27ac, Dox, rep1 |
GSM8268213 |
H3K27ac, Dox, rep2 |
GSM8268214 |
H3K27ac, Dox, rep3 |
GSM8268215 |
ATAC, no Dox, rep1 |
GSM8268216 |
ATAC, no Dox, rep2 |
GSM8268217 |
ATAC, Dox, rep1 |
GSM8268218 |
ATAC, Dox, rep2 |
GSM8268219 |
ATAC, Dox, rep3 |
GSM8268222 |
WT AIRE 4D6, no Dox, DMSO, rep1 |
GSM8268224 |
WT AIRE 4D6, no Dox, DMSO, rep2 |
GSM8268225 |
WT AIRE 4D6, no Dox, A-485, rep1 |
GSM8268226 |
WT AIRE 4D6, no Dox, A-485, rep2 |
GSM8268227 |
WT AIRE 4D6, 24hr Dox, DMSO, rep1 |
GSM8268228 |
WT AIRE 4D6, 24hr Dox, DMSO, rep2 |
GSM8268229 |
WT AIRE 4D6, 24hr Dox, A-485, rep1 |
GSM8268230 |
WT AIRE 4D6, 24hr Dox, A-485, rep2 |
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This SuperSeries is composed of the following SubSeries:
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GSE243822 |
Mechanism for controlled assembly of transcriptional condensates by Aire [RNA-seq] |
GSE243823 |
Mechanism for controlled assembly of transcriptional condensates by Aire [CRISPR] |
GSE243824 |
Mechanism for controlled assembly of transcriptional condensates by Aire [ChIP-seq] |
GSE267525 |
Mechanism for controlled assembly of transcriptional condensates by Aire [ATAC-seq] |
GSE267527 |
Mechanism for controlled assembly of transcriptional condensates by Aire [5'-ethynyl uridine RNA-seq] |
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Relations |
BioProject |
PRJNA1020110 |
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