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Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium.
- Source :
-
Development (Cambridge, England) [Development] 2015 Jun 15; Vol. 142 (12), pp. 2163-72. Date of Electronic Publication: 2015 May 28. - Publication Year :
- 2015
-
Abstract
- The DNA methyltransferase Dnmt1 maintains DNA methylation patterns and genomic stability in several in vitro cell systems. Ablation of Dnmt1 in mouse embryos causes death at the post-gastrulation stage; however, the functions of Dnmt1 and DNA methylation in organogenesis remain unclear. Here, we report that Dnmt1 is crucial during perinatal intestinal development. Loss of Dnmt1 in intervillus progenitor cells causes global hypomethylation, DNA damage, premature differentiation, apoptosis and, consequently, loss of nascent villi. We further confirm the crucial role of Dnmt1 during crypt development using the in vitro organoid culture system, and illustrate a clear differential requirement for Dnmt1 in immature versus mature organoids. These results demonstrate an essential role for Dnmt1 in maintaining genomic stability during intestinal development and the establishment of intestinal crypts.<br /> (© 2015. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Apoptosis genetics
Cell Proliferation genetics
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases genetics
DNA Damage genetics
Gene Expression Regulation, Developmental
Intestinal Mucosa cytology
Mice
Mice, Knockout
Molecular Sequence Data
DNA (Cytosine-5-)-Methyltransferases physiology
DNA Methylation genetics
Genomic Instability genetics
Intestinal Mucosa embryology
Organogenesis genetics
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 142
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 26023099
- Full Text :
- https://doi.org/10.1242/dev.117341