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| Status |
Public on Jul 04, 2024 |
| Title |
NAT10-mediated β-hydroxybutyrylation Rewires Genomic 3D Conformation and Replication Timing [Hi-C] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Spatiotemporal regulation of chromatin replication (replication timing, RT） in eukaryotes is critical to maintain the genomic integrity. Here we focused on epigenetic mechanisms in rewiring genomic 3D conformation and replication timing. The results show that the novel lysine β-hydroxybutyrylation (Kbhb) modifications accelerates chromatin replication without inducing replication defects. This effect was mediated by the NAT10, a novel b-hydroxybutyryl-transferase, through regulating the association of NAT10 and CTCF with chromatin. Depletion of NAT10 and NAT10-mediated Kbhb dramatically reduce chromatin-bound NAT10 and CTCF, resulting in reorganization of genomic 3D conformation with enhanced trans- and cis-interaction in Hi-C matrix, with elevated proportion of A compartments, and with reorganized TADs boundaries. Moreover, reorganization of genomic 3D conformation contributes to rewire replication timing. These results support models in which NAT10-mediated β-hydroxybutyrylation coordinates genomic 3D conformation reorganization with replication timing alteration, and emphatically address the concept that epigenetic mechanisms reconcile genomic 3D conformation with replication timing.
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| Overall design |
Hi-C sequencing was performed in two biological replicates on β-hydroxybutyrate (BHB) treated control (siCtrl) or NAT10 knock-down (siNAT10) U2OS cells.
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| Contributor(s) |
Zhao W, Liu K |
| Citation missing |
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| Submission date |
Jul 04, 2021 |
| Last update date |
Jul 04, 2024 |
| Contact name |
wenhui Zhao |
| E-mail(s) |
ZHAOWENHUI@CQU.EDU.CN
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| Organization name |
Peking University
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| Street address |
5 Yiheyuan Road, Haidian District
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| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA743646 |
| SRA |
SRP326860 |
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