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| Status |
Public on Jul 11, 2024 |
| Title |
Polymerization of BTB transcription factors regulates chromatin occupancy [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The broad-complex, tramtrack and bric-à-brac (BTB) family of transcription factors (TFs) serve as important regulators of hematopoietic development. The BTB domains of these TFs mediate co-repressor recruitment and dimerization, but their propensity to self-assemble into higher-order structures has not been established. Here, we survey 189 human BTB proteins and identify 18 BTB TFs that form punctate nuclear foci. We demonstrate that these foci-forming BTB TFs polymerize into filaments and present the cryo-EM structures of ZBTB5BTB and ZBTB9BTB filaments. Finally, we find that polymerization in BTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites. This increased chromatin occupancy in turn leads to the repression of target genes. Taken together, our results reveal a novel mechanism to regulate BTB TFs, and suggest an underappreciated role for polymerization in regulating TF function.
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| Overall design |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) was performed for ZBTB3 and ZBTB9 in HEK 293T cells modified to knock out endogenous ZBTB3 and ZBTB9 respectively. In each case, sequencing was performed across both doxycycline inducable over expression of wild-type (WT) ZBTB3/9 and non-polymerizing mutant (K166A for ZBTB3, W128A for ZBTB9) ZBTB3/ZBTB9. Samples were prepared in duplicate across 0.01, 0.1, and 1.0 ug/mL dosages of doxycycline. Fractions of each sample were sequenced absent precipitation as matched input datasets.
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| Contributor(s) |
Park PM, Park J, Brown J, Hunkeler M, Roy Burman SS, Donovan KA, Lumpkin RJ, Yoon H, Nowak RP, Słabicki M, Ebert BL, Fischer ES |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 20, 2023 |
| Last update date |
Jul 11, 2024 |
| Contact name |
Jared Brown |
| E-mail(s) |
jbrown@ds.dfci.harvard.edu
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| Organization name |
Dana Farber Cancer Institute
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| Department |
Data Science
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| Lab |
Irizarry
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| Street address |
Mailtop CLS11007, 450 Brookline Ave
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
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| Samples (48)
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| GSM7986010 |
293T WT-ZBTB3, Input, 0.1 Dox, rep2 |
| GSM7986011 |
293T WT-ZBTB3, Input, 1 Dox, rep1 |
| GSM7986012 |
293T WT-ZBTB3, Input, 1 Dox, rep2 |
| GSM7986013 |
293T K166A, Input, 0.01 Dox, rep1 |
| GSM7986014 |
293T K166A, Input, 0.01 Dox, rep2 |
| GSM7986015 |
293T K166A, Input, 0.1 Dox, rep1 |
| GSM7986016 |
293T K166A, Input, 0.1 Dox, rep2 |
| GSM7986017 |
293T K166A, Input, 1 Dox, rep1 |
| GSM7986018 |
293T K166A, Input, 1 Dox, rep2 |
| GSM7986019 |
293T WT-ZBTB3, ZBTB3, 0.01 Dox, rep1 |
| GSM7986020 |
293T WT-ZBTB3, ZBTB3, 0.01 Dox, rep2 |
| GSM7986021 |
293T WT-ZBTB3, ZBTB3, 0.1 Dox, rep1 |
| GSM7986022 |
293T WT-ZBTB3, ZBTB3, 0.1 Dox, rep2 |
| GSM7986023 |
293T WT-ZBTB3, ZBTB3, 1 Dox, rep1 |
| GSM7986024 |
293T WT-ZBTB3, ZBTB3, 1 Dox, rep2 |
| GSM7986025 |
293T K166A, ZBTB3, 0.01 Dox, rep1 |
| GSM7986026 |
293T K166A, ZBTB3, 0.01 Dox, rep2 |
| GSM7986027 |
293T K166A, ZBTB3, 0.1 Dox, rep1 |
| GSM7986028 |
293T K166A, ZBTB3, 0.1 Dox, rep2 |
| GSM7986029 |
293T K166A, ZBTB3, 1 Dox, rep1 |
| GSM7986030 |
293T K166A, ZBTB3, 1 Dox, rep2 |
| GSM7986031 |
293T WT-ZBTB9, Input, 0.01 Dox, rep1 |
| GSM7986032 |
293T WT-ZBTB9, Input, 0.01 Dox, rep2 |
| GSM7986033 |
293T WT-ZBTB9, Input, 0.1 Dox, rep1 |
| GSM7986034 |
293T WT-ZBTB9, Input, 0.1 Dox, rep2 |
| GSM7986035 |
293T WT-ZBTB9, Input, 1 Dox, rep1 |
| GSM7986036 |
293T WT-ZBTB9, Input, 1 Dox, rep2 |
| GSM7986037 |
293T W128A, Input, 0.01 Dox, rep1 |
| GSM7986038 |
293T W128A, Input, 0.01 Dox, rep2 |
| GSM7986039 |
293T W128A, Input, 0.1 Dox, rep1 |
| GSM7986040 |
293T W128A, Input, 0.1 Dox, rep2 |
| GSM7986041 |
293T W128A, Input, 1 Dox, rep1 |
| GSM7986042 |
293T W128A, Input, 1 Dox, rep2 |
| GSM7986043 |
293T WT-ZBTB9, ZBTB9, 0.01 Dox, rep1 |
| GSM7986044 |
293T WT-ZBTB9, ZBTB9, 0.01 Dox, rep2 |
| GSM7986045 |
293T WT-ZBTB9, ZBTB9, 0.1 Dox, rep1 |
| GSM7986046 |
293T WT-ZBTB9, ZBTB9, 0.1 Dox, rep2 |
| GSM7986047 |
293T WT-ZBTB9, ZBTB9, 1 Dox, rep1 |
| GSM7986048 |
293T WT-ZBTB9, ZBTB9, 1 Dox, rep2 |
| GSM7986049 |
293T W128A, ZBTB9, 0.01 Dox, rep1 |
| GSM7986050 |
293T W128A, ZBTB9, 0.01 Dox, rep2 |
| GSM7986051 |
293T W128A, ZBTB9, 0.1 Dox, rep1 |
| GSM7986052 |
293T W128A, ZBTB9, 0.1 Dox, rep2 |
| GSM7986053 |
293T W128A, ZBTB9, 1 Dox, rep1 |
| GSM7986054 |
293T W128A, ZBTB9, 1 Dox, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE251688 |
Polymerization of BTB transcription factors regulates chromatin occupancy |
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| Relations |
| BioProject |
PRJNA1055065 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE251687_RAW.tar |
10.7 Gb |
(http)(custom) |
TAR (of BED, BW) |
| GSE251687_ZBTB3_MergedPeakCounts.csv.gz |
843.4 Kb |
(ftp)(http) |
CSV |
| GSE251687_ZBTB3_MergedPeaks.bed.gz |
224.8 Kb |
(ftp)(http) |
BED |
| GSE251687_ZBTB3_SampleMetaData.csv.gz |
1.1 Kb |
(ftp)(http) |
CSV |
| GSE251687_ZBTB9_MergedPeakCounts.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
| GSE251687_ZBTB9_MergedPeaks.bed.gz |
284.0 Kb |
(ftp)(http) |
BED |
| GSE251687_ZBTB9_SampleMetaData.csv.gz |
1.1 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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