Broad Heterochromatic Domains Open in Gonocyte Development Prior to De Novo DNA Methylation
Facultative heterochromatin forms and reorganizes in response to external stimuli. However, how the initial establishment of such a chromatin state is regulated in cell-cycle-arrested cells remains unexplored. Mouse gonocytes are arrested male germ cells, at which stage the genome-wide DNA methylome...
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Published in | Developmental cell Vol. 51; no. 1; pp. 21 - 34.e5 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
07.10.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Facultative heterochromatin forms and reorganizes in response to external stimuli. However, how the initial establishment of such a chromatin state is regulated in cell-cycle-arrested cells remains unexplored. Mouse gonocytes are arrested male germ cells, at which stage the genome-wide DNA methylome forms. Here, we discovered transiently accessible heterochromatin domains of several megabases in size in gonocytes and named them differentially accessible domains (DADs). Open DADs formed in gene desert and gene cluster regions, primarily at transposons, with the reprogramming of histone marks, suggesting DADs as facultative heterochromatin. De novo DNA methylation took place with two waves in gonocytes: the first region specific and the second genome-wide. DADs were resistant to the first wave and their opening preceded the second wave. In addition, the higher-order chromosome architecture was reorganized with less defined chromosome compartments in gonocytes. These findings suggest that multiple layers of chromatin reprogramming facilitate de novo DNA methylation.
•Chromosomes in gonocytes contain differentially accessible domains (DADs)•Young LINE-1 elements in DADs become activated in the middle of the gonocyte stage•DADs are resistant to the first wave of de novo DNA methylation•3D chromosome organization is reprogrammed in gonocytes
Genome-wide de novo DNA methylation occurs in mouse gonocytes, arrested male embryonic germ cells. However, how the methylome gets established in the genome of arrested cells remains unexplored. Yamanaka et al. report that multiple chromatin reprogramming pathways allow the access of methyltransferases to DNA in gonocytes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1534-5807 1878-1551 |
DOI: | 10.1016/j.devcel.2019.07.023 |