| First Authors | Deepthi Ashokkumar, Qinyu Zhang |
|---|---|
| Authors | Deepthi Ashokkumar, Qinyu Zhang, Christian Much, Anita S. Bledau, Ronald Naumann, Dimitra Alexopoulou, Andreas Dahl, Neha Goveas, Jun Fu, Konstantinos Anastassiadis, A F Stewart, Andrea Kranz |
| Corresponding Authors | A F Stewart, Andrea Kranz |
| Last Authors | Andrea Kranz |
| Journal Name | Development (Cambridge, England) (Development) |
| Volume | 147 |
| Issue | 12 |
| Article Number | dev186999 |
| Open Access | false |
| Print Publication Date | 2020-06-17 |
| Online Publication Date | |
| Abstract | Methylation of histone 3 lysine 4 (H3K4) is a major epigenetic system associated with gene expression. In mammals there are six H3K4 methyltransferases related to yeast Set1 and fly Trithorax, including two orthologs of fly Trithorax-related: MLL3 and MLL4. Exome sequencing has documented high frequencies of MLL3 and MLL4 mutations in many types of human cancer. Despite this emerging importance, the requirements of these paralogs in mammalian development have only been incompletely reported. Here, we examined the null phenotypes to establish that MLL3 is first required for lung maturation, whereas MLL4 is first required for migration of the anterior visceral endoderm that initiates gastrulation in the mouse. This collective cell migration is preceded by a columnar-to-squamous transition in visceral endoderm cells that depends on MLL4. Furthermore, Mll4 mutants display incompletely penetrant, sex-distorted, embryonic haploinsufficiency and adult heterozygous mutants show aspects of Kabuki syndrome, indicating that MLL4 action, unlike MLL3, is dosage dependent. The highly specific and discordant functions of these paralogs in mouse development argues against their action as general enhancer factors. |
| Cover Image | |
| Affiliated With | Transgenic Core Facility |
| Selected By | Transgenic Core Facility |
| Acknowledged Services | |
| Publication Status | Published |
| Edoc Link | |
| Sfx Link | |
| DOI | 10.1242/dev.186999 |
| PubMed ID | 32439762 |
| WebOfScience Link | WOS:000567372300015 |
| Alternative Full Text URL | |
| Display Publisher Download Only | false |
| Visible On MPI-CBG Website | true |
| PDF Downloadable | true |
| Created By | naumann |
| Added Date | 2020-05-23 |
| Last Edited By | herbst |
| Last Edited Date | 2021-06-21 17:32:16.871 |
| Library ID | 7678 |
| Document ID | |
| Entry Complete | true |
| eDoc Compliant | true |
| Include in Edoc Report | true |
| In Pure | true |
| Ready for eDoc Export | false |
| Author Affiliations Complete | false |
| Project Name | |
| Project URL | |
| Grant ID | |
| Funding Programme | |
| Funding Organisation |