Continuous histone replacement by Hira is essential for normal transcriptional regulation and efficient de novo DNA methylation during mouse oogenesis
| Autor: | Gopuraja Dharmalingam, Petra Hajkova, Elodie Ndjetehe, Sébastien A. Smallwood, Peter W. S. Hill, Gavin Kelsey, Rachel Amouroux, Stephen J. Clark, Richard Festenstein, Pawel Pelczar, Buhe Nashun, Vineet Sharma |
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| Přispěvatelé: | Commission of the European Communities, EMBO, Medical Research Council (MRC), Clark, Stephen James [0000-0002-6183-491X], Kelsey, Gavin [0000-0002-9762-5634], Apollo - University of Cambridge Repository |
| Rok vydání: | 2015 |
| Předmět: |
CHROMATIN
Biochemistry & Molecular Biology Transcription Genetic Cell Cycle Proteins Biology NUCLEOSOME Chromatin remodeling OOCYTE Histones Mice Oogenesis Histone H1 CHAPERONE HIRA Histone methylation Histone H2A Histone code Animals Histone Chaperones Molecular Biology 11 Medical and Health Sciences Epigenomics GENE-EXPRESSION Science & Technology LANDSCAPE Cell Biology DNA Methylation 06 Biological Sciences Molecular biology Chromatin Gene Expression Regulation Histone methyltransferase Fertilization PREIMPLANTATION DEVELOPMENT REPLICATION Oocytes TURNOVER Female Life Sciences & Biomedicine VARIANT H3.3 Transcription Factors Developmental Biology |
| Popis: | The integrity of chromatin, which provides a dynamic template for all DNA-related processes in eukaryotes, is maintained through replication-dependent and -independent assembly pathways. To address the role of histone deposition in the absence of DNA replication, we deleted the H3.3 chaperone Hira in developing mouse oocytes. We show that chromatin of non-replicative developing oocytes is dynamic and that lack of continuous H3.3/H4 deposition alters chromatin structure, resulting in increased DNase I sensitivity, the accumulation of DNA damage, and a severe fertility phenotype. On the molecular level, abnormal chromatin structure leads to a dramatic decrease in the dynamic range of gene expression, the appearance of spurious transcripts, and inefficient de novo DNA methylation. Our study thus unequivocally shows the importance of continuous histone replacement and chromatin homeostasis for transcriptional regulation and normal developmental progression in a non-replicative system in vivo. |
| Databáze: | OpenAIRE |
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