English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis

Kang, J., Lienhard, M., Pastor, W. A., Chawla, A., Novotny, M., Tsagaratou, A., et al. (2015). Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis. Proceedings of the National Academy of Sciences of the United States of America, 112(31), E4236-E4245. doi:10.1073/pnas.1510510112.

Item is

Files

show Files
hide Files
:
Kang.pdf (Publisher version), 3MB
Name:
Kang.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2015 National Academy of Sciences
License:
-

Locators

show
hide
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Kang, J., Author
Lienhard, M.1, Author           
Pastor, W. A., Author
Chawla, A., Author
Novotny, M., Author
Tsagaratou, A., Author
Lasken, R. S., Author
Thompson, E. C., Author
Surani, M. A., Author
Koralov, S. B., Author
Kalantry, S., Author
Chavez, L., Author
Rao, A., Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385701              

Content

show
hide
Free keywords: 5-Methylcytosine/*metabolism Animals Biomarkers/metabolism Blastocyst/metabolism Blastomeres/metabolism/pathology Cell Lineage Cholesterol/biosynthesis DNA/metabolism DNA-Binding Proteins/deficiency/genetics/*metabolism Down-Regulation/genetics Embryo Loss/metabolism/pathology Embryo, Mammalian/pathology Embryonic Development/*genetics *Gene Deletion *Gene Expression Regulation, Developmental Genomic Imprinting Hedgehog Proteins/metabolism Mice, Inbred C57BL Mice, Knockout Proto-Oncogene Proteins/deficiency/genetics/*metabolism Repetitive Sequences, Nucleic Acid/genetics Sequence Analysis, RNA Signal Transduction/genetics Transcriptome/*genetics 5-hydroxymethylcytosine 5hmC DNA methylation TET methylcytosine oxidases cholesterol biosynthesis
 Abstract: Dioxygenases of the TET (Ten-Eleven Translocation) family produce oxidized methylcytosines, intermediates in DNA demethylation, as well as new epigenetic marks. Here we show data suggesting that TET proteins maintain the consistency of gene transcription. Embryos lacking Tet1 and Tet3 (Tet1/3 DKO) displayed a strong loss of 5-hydroxymethylcytosine (5hmC) and a concurrent increase in 5-methylcytosine (5mC) at the eight-cell stage. Single cells from eight-cell embryos and individual embryonic day 3.5 blastocysts showed unexpectedly variable gene expression compared with controls, and this variability correlated in blastocysts with variably increased 5mC/5hmC in gene bodies and repetitive elements. Despite the variability, genes encoding regulators of cholesterol biosynthesis were reproducibly down-regulated in Tet1/3 DKO blastocysts, resulting in a characteristic phenotype of holoprosencephaly in the few embryos that survived to later stages. Thus, TET enzymes and DNA cytosine modifications could directly or indirectly modulate transcriptional noise, resulting in the selective susceptibility of certain intracellular pathways to regulation by TET proteins.

Details

show
hide
Language(s): eng - English
 Dates: 2015-07-212015-08-04
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1073/pnas.1510510112
ISSN: 1091-6490 (Electronic)0027-8424 (Print)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
  Abbreviation : PNAS
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 112 (31) Sequence Number: - Start / End Page: E4236 - E4245 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230