LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo
Autor: | Joanna W. Jachowicz, Ana Bošković, Julien Pontabry, Oliver J. Rando, Maria-Elena Torres-Padilla, Xinyang Bing |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Transcription Genetic Zygote Embryonic Development Retrotransposon Biology Chromatin remodeling Embryo Culture Techniques Mice 03 medical and health sciences 0302 clinical medicine Transcription Activator-Like Effector Nucleases Genetics Animals Humans Medicine Gene silencing Gene Silencing RNA Messenger Crosses Genetic Epigenomics Regulation of gene expression business.industry Totipotent Gene Expression Regulation Developmental Obstetrics and Gynecology Embryo General Medicine Blastula Microfluidic Analytical Techniques Chromatin Assembly and Disassembly Chromatin Cell biology Mice Inbred C57BL Long Interspersed Nucleotide Elements 030104 developmental biology Fertilization Mice Inbred CBA Female business Reprogramming 030217 neurology & neurosurgery |
Zdroj: | Nature Genetics. 49:1502-1510 |
ISSN: | 1546-1718 1061-4036 |
DOI: | 10.1038/ng.3945 |
Popis: | After fertilization, to initiate development, gametes are reprogramed to become totipotent. Approximately half of the mammalian genome consists of repetitive elements, including retrotransposons, some of which are transcribed after fertilization. Retrotransposon activation is generally assumed to be a side effect of the extensive chromatin remodeling underlying the epigenetic reprogramming of gametes. Here, we used a targeted epigenomic approach to address whether specific retrotransposon families play a direct role in chromatin organization and developmental progression. We demonstrate that premature silencing of LINE-1 elements decreases chromatin accessibility, whereas prolonged activation prevents the gradual chromatin compaction that occurs naturally in developmental progression. Preventing LINE-1 activation and interfering with its silencing decreases developmental rates independently of the coding nature of the LINE-1 transcript, thus suggesting that LINE-1 functions primarily at the chromatin level. Our data suggest that activation of LINE-1 regulates global chromatin accessibility at the beginning of development and indicate that retrotransposon activation is integral to the developmental program. |
Databáze: | OpenAIRE |
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