|
| Status |
Public on Aug 10, 2023 |
| Title |
CaBlCaXi: MSL2 is an allelic dosage sensor in mammals |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Allele-specific gene expression have been observed in genomic imprinting, X chromosome inactivation, allelic exclusion of immunoglobulin loci and non-canonical random monoallelic expression. Here we show that MSL2 can regulate allele specific gene expression and we elucidate its mechanism of action. MSL2 is known to regulate gene dosage up to two fold in drosophila and mammals. In addition to its canonical role as a milder modulator, we found that the loss of MSL2 switches off gene expression completely in an allele specific way and results in biallelic to monoallelic gene expression, which will be ignored as classical down regulated genes without applying the mouse hybrid F1 system. It indicates that MSL2 can activate the expression of the allele which is otherwise inactive intrinsically. We further found this is achieved by the interplay between MSL and KANSL complex. MSL2 acts as a methylation-insensitive factor, which can prevent DNA methylation of the inactive allele, thus facilitating occupancy of methylation-sensitive factor KANSL3 and activating the gene expression. The novel mechanism of MSL2 provides a safeguarding system to warrant biallelic gene expression of intrinsically monoallelic expressed genes including X-inactivated and imprinting genes. These genes are further discovered as sex bias genes such as X-inactivation escaped genes (escapees) are expressed higher in females. Furthermore, the biallelic expression of MSL2 regulated escapees may protect females from single loss of function mutation and contribute to male severer or predominance neurodevelopmental diseases.
|
| |
|
| Overall design |
Allele specific differential analysis of various sequencing data from ESCs and NPCs of female and male hybrid clones.
|
| |
|
| Contributor(s) |
Sun Y, Hmad R, Wiese M, Akhtar A |
| Citation(s) |
38030723 |
| |
| Submission date |
Mar 20, 2023 |
| Last update date |
Dec 14, 2023 |
| Contact name |
Asifa Akhtar |
| E-mail(s) |
akhtarlab_data@ie-freiburg.mpg.de
|
| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Department |
Chromatin Regulation
|
| Lab |
Akhtar Lab
|
| Street address |
Stuebeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE183556 |
MSL2 is an allelic dosage sensor in mammals |
|
| Relations |
| BioProject |
PRJNA946739 |
Less...
More...