Dynamic changes in histone modifications precede de novo DNA methylation in oocytes.

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dc.creatorStewart, Kathleen R
dc.creatorVeselovska, Lenka
dc.creatorKim, Jeesun
dc.creatorHuang, Jiahao
dc.creatorSaadeh, Heba
dc.creatorTomizawa, Shin-ichi
dc.creatorSmallwood, Sébastien A
dc.creatorChen, Taiping
dc.creatorKelsey, Gavin
dc.date2019-06-24T23:31:28Z
dc.date2019-06-24T23:31:28Z
dc.date2015-12-01
dc.date.accessioned2026-08-03T03:57:43Z
dc.descriptionErasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.
dc.formatPrint-Electronic
dc.formatapplication/pdf
dc.identifier0890-9369
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/293946
dc.identifier10.17863/CAM.41054
dc.identifier1549-5477
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/183154
dc.languageeng
dc.languageeng
dc.publisherCold Spring Harbor Laboratory
dc.publisherhttps://doi.org/10.1101/gad.271353.115
dc.rightsAttribution-NonCommercial 4.0 International
dc.rightshttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectChIP-seq
dc.subjectDNA methylation
dc.subjectgenomic imprinting
dc.subjecthistone modifications
dc.subjectoocytes
dc.subjectAnimals
dc.subjectChromatin Immunoprecipitation
dc.subjectCpG Islands
dc.subjectDNA Methylation
dc.subjectFlow Cytometry
dc.subjectHistone Code
dc.subjectHistone Demethylases
dc.subjectHistones
dc.subjectMice
dc.subjectOocytes
dc.subjectOogenesis
dc.subjectOxidoreductases, N-Demethylating
dc.subjectSequence Analysis, DNA
dc.titleDynamic changes in histone modifications precede de novo DNA methylation in oocytes.
dc.typeArticle

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