Journal Article

DKFZ-2017-02841

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. ; Lasken, R. S. ; Thompson, E. C. ; Surani, M. A. ; Koralov, S. B. ; Kalantry, S. ; Chavez, L.DKFZ* ; Rao, A.

2015
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1510510112

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.

Keyword(s): Biomarkers ; DNA-Binding Proteins ; Hedgehog Proteins ; Proto-Oncogene Proteins ; Shh protein, mouse ; TET1 protein, mouse ; Tet3 protein, mouse ; 5-Methylcytosine ; DNA ; Cholesterol

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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