Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium

Ellen N. Elliott; Karyn L. Sheaffer; Jonathan Schug; Thaddeus S. Stappenbeck; Klaus H. Kaestner

doi:10.1242/dev.117341

Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium

Ellen N. Elliott
, Karyn L. Sheaffer
, Jonathan Schug
, Thaddeus S. Stappenbeck
, Klaus H. Kaestner

Division of Laboratory and Genomic Medicine

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

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 postgastrulation 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 confirmthe 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.

Original language	English
Pages (from-to)	2163-2172
Number of pages	10
Journal	Development (Cambridge)
Volume	142
Issue number	12
DOIs	https://doi.org/10.1242/dev.117341
State	Published - Jun 15 2015

Keywords

DNA damage response
DNA methylation
Intestinal epithelial development

Access to Document

10.1242/dev.117341

Cite this

@article{eaa094db953c4eb699d385943d00debd,

title = "Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium",

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 postgastrulation 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 confirmthe 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.",

keywords = "DNA damage response, DNA methylation, Intestinal epithelial development",

author = "Elliott, \{Ellen N.\} and Sheaffer, \{Karyn L.\} and Jonathan Schug and Stappenbeck, \{Thaddeus S.\} and Kaestner, \{Klaus H.\}",

note = "Publisher Copyright: {\textcopyright} 2015. Published by The Company of Biologists Ltd.",

year = "2015",

month = jun,

day = "15",

doi = "10.1242/dev.117341",

language = "English",

volume = "142",

pages = "2163--2172",

journal = "Development (Cambridge)",

issn = "0950-1991",

number = "12",

}

TY - JOUR

T1 - Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium

AU - Elliott, Ellen N.

AU - Sheaffer, Karyn L.

AU - Schug, Jonathan

AU - Stappenbeck, Thaddeus S.

AU - Kaestner, Klaus H.

PY - 2015/6/15

Y1 - 2015/6/15

N2 - 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 postgastrulation 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 confirmthe 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.

AB - 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 postgastrulation 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 confirmthe 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.

KW - DNA damage response

KW - DNA methylation

KW - Intestinal epithelial development

UR - https://www.scopus.com/pages/publications/84931056085

U2 - 10.1242/dev.117341

DO - 10.1242/dev.117341

M3 - Article

C2 - 26023099

AN - SCOPUS:84931056085

SN - 0950-1991

VL - 142

SP - 2163

EP - 2172

JO - Development (Cambridge)

JF - Development (Cambridge)

IS - 12

ER -

Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this