Projects per year
Abstract
Methylation of DNA at carbon 5 of cytosine is essential for mammalian development and implicated in transcriptional repression of genes and transposons. New patterns of DNA methylation characteristic of lineage-committed cells are established at the exit from pluripotency by de novo DNA methyltransferases enzymes, DNMT3A and DNMT3B, which are regulated by developmental signalling and require access to chromatin-organised DNA. Whether or not the capacity for de novo DNA methylation of developmentally regulated loci is preserved in differentiated somatic cells and can occur in the absence of exogenous signals is currently unknown. Here we demonstrate that fibroblasts derived from chromatin remodelling ATPase LSH (HELLS)-null mouse embryos, which lack DNA methylation from centromeric repeats, transposons and a number of gene promoters, are capable of re-establishing DNA methylation and silencing of miss-regulated genes upon re-expression of LSH. We also show that the ability of LSH to bind ATP and the cellular concentration of DNMT3B are critical for cell-autonomous de novo DNA methylation in somatic cells. These data suggest the existence of cellular memory that persists in differentiated cells through many cell generations and changes in transcriptional state.
Original language | English |
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Journal | Nucleic Acids Research |
Early online date | 13 May 2016 |
DOIs | |
Publication status | Published - 19 Sept 2016 |
Keywords / Materials (for Non-textual outputs)
- epigenetics
- DNA methylation
- chromatin
- gene silencing
- LSH
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Dive into the research topics of 'The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells'. Together they form a unique fingerprint.Projects
- 3 Finished
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Core funding renewal for the Wellcome Trust Centre for Cell Biology
Tollervey, D. (Principal Investigator) & Earnshaw, B. (Co-investigator)
1/10/11 → 30/04/17
Project: Research
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Establishment and maintenance of cancer-specific DNA methylation patterns by chromatin remodelling protein LSH
Stancheva, I. (Principal Investigator)
1/10/08 → 30/09/12
Project: Research
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Epigenetic gene silencing in normal cells and cancer
Stancheva, I. (Principal Investigator)
1/04/08 → 30/09/14
Project: Research