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Status |
Public on Aug 31, 2024 |
Title |
Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation |
Organism |
Homo sapiens |
Experiment type |
Other
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Summary |
FOXA1 serves as a crucial pioneer transcription factor in developmental processes, and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites, however, the regulatory mechanisms governing FOXA1's molecular dynamics in mitosis remain elusive. Here we show that mitotic kinase Aurora B regulates FOXA1's different DNA binding modes and the formation of the biomolecular condensate. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to disrupt the specific, but not the non-specific, DNA binding. The phosphorylation of S221 also negatively regulates the FOXA1 condensates that require specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivations and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.
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Overall design |
CUT&Tag sequencing for FOXA1 wild-type and FOXA1 S221A in interphase and mitotic stably expressing GFP-FOXA1 wild-type and S221A HeLa cell
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Contributor(s) |
Zhang T, Liu S, Liu X, Yao X |
Citation missing |
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Submission date |
Aug 01, 2024 |
Last update date |
Aug 31, 2024 |
Contact name |
张 婷 |
E-mail(s) |
jocelynz@mail.ustc.edu.cn
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Phone |
18895364168
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Organization name |
中国科学技术大学
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Street address |
安徽省合肥市蜀山区黄山路443号中国科学技术大学西校区生命科学学院547室
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City |
hefei |
State/province |
Select an option… |
ZIP/Postal code |
230027 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (7)
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GSM8436518 |
Interphase HeLa, GFP, control, CUT&Tag (C1) |
GSM8436519 |
Interphase HeLa, GFP-FOXA1, WT-group1, CUT&Tag (K3) |
GSM8436520 |
Interphase HeLa, GFP-FOXA1, WT-group2, CUT&Tag (K4) |
GSM8436521 |
Mitosis HeLa, GFP-FOXA1, S221A-group1, CUT&Tag (K5) |
GSM8436522 |
Mitosis HeLa, GFP-FOXA1, S221A-group2, CUT&Tag (K6) |
GSM8436523 |
Mitosis HeLa, GFP-FOXA1, WT-group1, CUT&Tag (K7) |
GSM8436524 |
Mitosis HeLa, GFP-FOXA1, WT-group2, CUT&Tag (K8) |
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Relations |
BioProject |
PRJNA1142976 |
Supplementary file |
Size |
Download |
File type/resource |
GSE273759_RAW.tar |
250.3 Mb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
Raw data are available in SRA |
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