Abstract：
:The DNMT1 cytosine methyltransferase enzyme contains a large ∼300-aa intrinsically disordered domain (IDD) that we previously showed regulated DNA methylation patterns in mouse ES cells. Here we generated seven mouse lines with different mutations in the IDD. Homozygous mutant mice of five lines developed normally, with normal levels of methylation on both imprinted and nonimprinted DNA sequences. The other two lines, however, had alterations in imprinted and/or nonimprinted (global) DNA methylation appearing during embryonic development. Embryos of one line expressing a DNMT1 variant containing a 6-aa rat orthologous sequence in the IDD maintained imprinted methylation, showed very reduced levels of global methylation and occasionally completed fetal development. These in vivo studies demonstrate that at least two DNMT1-dependent methylation processes can be distinguished during fetal development. One process maintains the bulk of genomic methylation on nonimprinted sequences. The other process maintains methylation on a much smaller class of sequences including but not limited to gametic differentially methylated domains (gDMDs) that transmit essential imprinted parent-specific methylation for embryonic development.
journal_name
Geneticsjournal_title
Geneticsauthors
Shaffer B,McGraw S,Xiao SC,Chan D,Trasler J,Chaillet JRdoi
10.1534/genetics.114.173609subject
Has Abstractpub_date
2015-02-01 00:00:00pages
533-41issue
2eissn
0016-6731issn
1943-2631pii
genetics.114.173609journal_volume
199pub_type
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