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| Status |
Public on May 15, 2024 |
| Title |
MBD5, a m5C RNA reader, regulates histone ubiquitylation in development and function |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Methyl-CpG-binding domain (MBD)-containing proteins are readers of epigenetic information. The founding member, MeCP2, mutated in the Rett Syndrome, binds to methylated CpG DNAs. MBD5 is an evolutionarily conserved MBD family member associated with epilepsy, autism spectrum disorders (ASD), and early onset dementia. The mechanism of action of MBD5 remains unclear. Here we report that mbd5 regulates embryonic development, erythrocyte differentiation, iron metabolism, and behavior in zebrafish. MBD5 is essential to activate the expression of erythrocyte differentiation genes (e.g., hbae3), iron-regulated genes (e.g., fth1), and ASD-related genes (e.g., gabbr2), by binding to 5-methylcytosine (m5C) modified mRNAs, interacting with and stabilizing Additional Sex Combs Like 1 (ASXL1), a component of the Polycomb Repressive Deubiquinase (PR-DUB) complex, to facilitate removal of the repressive monoubiquitin mark at histone H2A (H2A-K119Ub), thereby facilitating gene activation. Together, these findings reveal MBD5 as a m5C RNA reader that links RNA methylation to histone modification in vivo.
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| Overall design |
[Dataset 1] 6 samples. Triplicates for ribo-minus RNA-Seq from 78 hpf zebrafish embryos treated with control or mbd5 morpholino
[Dataset 2] 16 samples. Duplicates for CLIP-seq experiments from 48-78 hpf zebrafish embryos treated with 0.5 mM DFO or 1 mM FAC
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| Contributor(s) |
Zou Z, Dou X, He C |
| Citation(s) |
38366571 |
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| Submission date |
Jan 12, 2023 |
| Last update date |
May 15, 2024 |
| Contact name |
Chuan He |
| E-mail(s) |
chuanhe@uchicago.edu
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| Organization name |
University of Chicago
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| Street address |
929 E 57th St, Room E319B
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| City |
Chicago |
| State/province |
Illinois |
| ZIP/Postal code |
60637 |
| Country |
USA |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA923391 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE222803_Mbd5_CLIP_peaks.xlsx |
5.0 Mb |
(ftp)(http) |
XLSX |
| GSE222803_mbd5MO_differentialExpression.xlsx |
993.2 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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