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MLL4 is required after implantation, whereas MLL3 becomes essential during late gestation.
- Source :
-
Development (Cambridge, England) [Development] 2020 Jun 17; Vol. 147 (12). Date of Electronic Publication: 2020 Jun 17. - Publication Year :
- 2020
-
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.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2020. Published by The Company of Biologists Ltd.)
- Subjects :
- Abnormalities, Multiple genetics
Abnormalities, Multiple pathology
Abnormalities, Multiple veterinary
Alleles
Animals
Embryo, Mammalian metabolism
Embryonic Development
Face abnormalities
Face pathology
Female
Genotype
Hematologic Diseases genetics
Hematologic Diseases pathology
Hematologic Diseases veterinary
Histone-Lysine N-Methyltransferase chemistry
Histone-Lysine N-Methyltransferase genetics
Lung growth & development
Lung metabolism
Male
Mice
Mice, Knockout
Mutagenesis
Pregnancy
Respiratory Insufficiency etiology
Time Factors
Vestibular Diseases genetics
Vestibular Diseases pathology
Vestibular Diseases veterinary
Histone-Lysine N-Methyltransferase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 147
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 32439762
- Full Text :
- https://doi.org/10.1242/dev.186999