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Series GSE92366 Query DataSets for GSE92366
Status Public on Mar 31, 2017
Title H3K4 Methylation-Mediated Memory of an Active Transcriptional State Impairs Nuclear Reprogramming
Organism Xenopus laevis
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Xenopus eggs can induce the reversal of differentiation processes of somatic cells. Yet, the egg is not fully efficient in reprogramming a differentiated nucleus, as certain genes retain a memory of gene expression of their somatic cell of origin. This is thought to be a reason for the low success rate of current cloning and reprogramming strategies. While previous studies addressed extensively the mechanisms that maintain an inactive state of genes (OFF-memory), we investigated the importance of memory of an active transcriptional state (ON-memory) in maintaining cell fate identity and on resistance to reprogramming. We find that donor cell-type specific ON-memory gene-expression in the wrong cell-type of nuclear transfer (NT)-embryos is as common as OFF-memory gene-expression. When compared to properly reprogrammed genes, we find that ON-memory genes show an elevated level of the active histone mark H3K4me3 in endoderm donor cells. Importantly, we show that a reduction of H3K4 methylation level in donor cells decreases the extent of ON-memory gene expression, globally improves transcriptional reprogramming, and enhances the development of NT-embryos. Therefore, our study reveals that H3K4 methylation safeguards endoderm cell identity and acts as a major barrier for efficient reprogramming in NT-embryos. Furthermore, our results suggest that efficient cell fate reprogramming not only relies on the erasure of epigenetic modifications conferring OFF-memory but also crucially depends on the removal of H3 lysine 4 methylation-mediated memory of an active state of gene expression.
Overall design 73 samples, single-ended RNA-seq libraries from neurula stage 18 or 21 endoderm and gastrula stage 11 ectoderm samples; 2 single-ended ChIP-seq libraries from endoderm cells of neurula (stage 21) embryos with antibody for H3K4me3, 2 replicates for each histone modification pull-down.
Contributor(s) Hörmanseder E, Simeone A, Allen GE, Bradshaw CR, Figlmüller M, Jullien J, Gurdon JB
Citation(s) 28366589
Submission date Dec 13, 2016
Last update date May 15, 2019
Contact name Angela Simeone
Organization name University of Cambridge
Department Cancer Research UK Cambridge Institute
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
Platforms (1)
GPL21046 Illumina HiSeq 1500 (Xenopus laevis)
Samples (77)
GSM2428182 Endoderm_Donor_1 (Group1)
GSM2428183 Ectoderm_IVF_1 (Group1)
GSM2428184 Ectoderm_IVF_2 (Group1)
BioProject PRJNA357356
SRA SRP095083

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE92366_Eva_HiSeq1500_2.Index15_vs_Eva_HiSeq1500_2.Index13_broad_peaks.bed.gz 654.1 Kb (ftp)(http) BED
GSE92366_IP36_H3K4me3_B_MF_vs_Input12_B_MF_broad_peaks.bed.gz 698.7 Kb (ftp)(http) BED
GSE92366_RAW.tar 19.8 Mb (http)(custom) TAR (of XLS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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