Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Epigenetic regulation of pre implantation development

ABSTRACT: Pre-implantation development is exemplified by extensive transcriptional and epigenetic changes, including zygotic genome activation, chromatin remodelling and global DNA demethylation. Excitingly, the advent of single-cell technologies will enable unprecedented high-resolution transcriptional and epigenetic profiling of this critical developmental stage. Furthermore, through the development of an in vitro model system I will identify key totipotency regulators, develop mechanistic insight into their mode of action and link these findings to somatic reprogramming. This study involves the use of RNA-sequencing (polyA+, ribominus and single-cell), ChIP-Sequencing and bisulfite sequencing.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): mus musculus

SUBMITTER:

PROVIDER: E-ERAD-370 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:During early stages of embryonic development the genome is transcriptionally inactive and cells are under the control of maternally provided mRNA and proteins. At a key point in development, known as the maternal to zygotic transition (MZT), the genome becomes activated and the maternally provided mRNAs begin to degrade. In the early zebrafish embryo, when under maternal control, cells divide rapidly and synchronously with cell cycles that lack gap phases. At cell cycle ten the introduction of gap phases lengthens the cell cycle and synchronised division is lost. During the MZT, zygotic activation of microRNAs leads to the targeted degradation of a number of maternally provided mRNAs, thus linking genome activation to maternal mRNA degredation.While the MZT has been studied in several different organisms the molecular mechanisms that coordinate genome activity and mRNA degradation remain largely unknown. For example, while the bulk of zygotic transcription occurs at cell cycle ten we do not understand why there is a minor wave of transcription before this time point. Similarly maternal mRNAs degrade at different rates, with only a percentage undergoing microRNA-mediated degredation. The aparant different rates of maternal mRNA degredation may be obscured by zygotic transcription.In order to gain an understanding of the MZT I intend to establish a precise understanding of transcription in the early embryo by using solexa sequencing to perform transcript counting at five different developmental stages that span the MZT. Specifically I intend to use crosses from two different zebrafish strains SAT (Sequenced AB and Tbingen, Zv9) and WIK. This project will allow one to understand the overall transcription profiles of genes in the early embryo, but importantly, the SNPs between the two different strains will determine if transcripts are maternal or zygotic (paternal). As a proof of principle we will first use one lane of sequencing to identify transcripts from a cross of an SAT and a WIK fish. This will allow us to observe SNPs between the two different strains. This will be run over one solexa lane. We will then sequence from five different time points on four different crosses SAT male and WIK female, WIK male and SAT female, WIK male and WIK female and SAT male with SAT female. We will prepare the libraries, which will be sequenced paired-end 54 bp over a total of seven lanes of solexa.. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

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Epigenetic regulation of pre implantation development

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