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| Status |
Public on Apr 26, 2024 |
| Title |
MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mutations in the methyl-DNA-binding protein MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). How MECP2 contributes to transcriptional regulation in normal and disease states is unresolved; it has been reported to be an activator and a repressor. We describe here the first integrated CUT&Tag, transcriptome, and proteome analyses using human neurons with wild-type and mutant MECP2 molecules. MECP2 occupies CpG-rich promoter-proximal regions in over four thousand genes in human neurons, including a plethora of autism risk genes, together with RNA polymerase II (Pol II). MECP2 directly interacts with Pol II, and genes occupied by both proteins showed reduced expression in neurons with MECP2 patient mutations. We conclude that MECP2 acts as a positive cofactor for Pol II gene expression at many neuronal genes that harbor CpG-islands in promoter-proximal regions, and that RTT is due, in part, to the loss of gene activity at these genes in neurons.
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| Overall design |
We used ATAC-Seq (Assay for Transposase-Accessible Chromatin using Sequencing), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid epigenomic analysis to identify open chromatin regions in human neurons.
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| Contributor(s) |
Liu Y, Flamier A, Bell GW, Whitfield TW, Young RA, Jaenisch R |
| Citation missing |
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| Submission date |
Mar 12, 2024 |
| Last update date |
Apr 26, 2024 |
| Contact name |
Yi Liu |
| E-mail(s) |
yiliu@wi.mit.edu
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| Phone |
6173010107
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| Organization name |
Whitehead Institute for Biomedical Research
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| Lab |
Jaenisch lab
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| Street address |
455 Main St
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02141 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE230716 |
MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons |
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| Relations |
| BioProject |
PRJNA1086987 |
