VUmc - CCA Genome Core
Ontology highlight
ABSTRACT:
PROVIDER: EGAO00000000238 | EGA |
REPOSITORIES: EGA
Publications
MiR expression profiles of paired primary colorectal cancer and metastases by next-generation sequencing.
Neerincx M M Sie D L S DL van de Wiel M A MA van Grieken N C T NC Burggraaf J D JD Dekker H H Eijk P P PP Ylstra B B Verhoef C C Meijer G A GA Buffart T E TE Verheul H M W HM
Oncogenesis 20151005
MicroRNAs (miRs) have been recognized as promising biomarkers. It is unknown to what extent tumor-derived miRs are differentially expressed between primary colorectal cancers (pCRCs) and metastatic lesions, and to what extent the expression profiles of tumor tissue differ from the surrounding normal tissue. Next-generation sequencing (NGS) of 220 fresh-frozen samples, including paired primary and metastatic tumor tissue and non-tumorous tissue from 38 patients, revealed expression of 2245 known ...[more]
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2017-09-25 | E-MTAB-3983 | biostudies-arrayexpress
Project description:CCA-adding enzymes are polymerases existing in two distinct enzyme classes that both synthesize the C-C-A triplet at tRNA 3'-ends. Class II enzymes (found in bacteria and eukaryotes) carry a flexible loop in their catalytic core required for switching the specificity of the nucleotide binding pocket from CTP- to ATP-recognition. Despite this important function, the loop sequence varies strongly between individual class II CCA-adding enzymes. To investigate whether this loop operates as a discrete functional entity or whether it depends on the sequence context of the enzyme, we introduced reciprocal loop replacements in several enzymes. Surprisingly, many of these replacements are incompatible with enzymatic activity and inhibit ATP-incorporation. A phylogenetic analysis revealed the existence of conserved loop families. Loop replacements within families did not interfere with enzymatic activity, indicating that the loop function depends on a sequence context specific for individual enzyme families. Accordingly, modeling experiments suggest specific interactions of loop positions with important elements of the protein, forming a lever-like structure. Hence, although being part of the enzyme's catalytic core, the loop region follows an extraordinary evolutionary path, independent of other highly conserved catalytic core elements, but depending on specific sequence features in the context of the individual enzymes.
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Project description:Double homeobox 4 (DUX4) is expressed in at the early preimplantation stage in human embryos. Here we show that induced human DUX4 expression substantially alters the non-coding chromatin accessibility of non-coding DNA and activates thousands of newly identified putative transcribed enhancer-like regions, preferentially located within ERVL-MaLR repeat elements. CRISPR activation of transcribed enhancers by C-terminal DUX4 motifs results in the increased expression of target embryonic genome activation (EGA) genes ZSCAN4 and KHDC1P1. We show that DUX4 is markedly enriched in human zygotes, followed by intense nuclear DUX4 localization preceding and coinciding with minor EGA. DUX4 knockdown in human zygotes led to changes in the EGA transcriptome but did not terminate the embryos. We also show that the DUX4 protein interacts with the Mediator complex via the C-terminal KIX binding motif. Our findings contribute to the understanding of DUX4 as a regulator of the non-coding genome.
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Project description:Reprogramming of histone modification regulates gene expression and mammal preimplantation development. Trimethylation of lysine 4 on histone 3 (H3K4me3) has unique landscape in mouse oocytes and early embryos. However, the dynamics and function of H3K4me3 in livestock embryos remain unclear. To address how it is reprogrammed in domestic animals, we profiled changes of H3K4me3 during bovine early embryo development. Notably, the overall signal of H3K4me3 decreased during embryonic genome activation (EGA). By utilizing ultra-low-input native ChIP-seq (ULI-NChIP-seq) technology, we observed widespread broad H3K4me3 domains in oocytes and embryos. The signal of broad H3K4me3 began to decrease after fertilization and was lowest after EGA. Along with the removal of broad H3K4me3, deposition of H3K4me3 at promoter regions enhanced gradually. Besides, the transcriptional activity and signal of promoter H3K4me3 showed positive correlation after the erasure of broad H3K4me3 at 16-cell stage. Moreover, knocking down of demethylases KDM5A, KDM5B and KDM5C caused EGA delay and blastocyst formation failure. RNA-seq analysis revealed 47.8% down-regulated genes in knockdown embryos at 8/16-cell stage were EGA genes, and 63.1% of up-regulated genes were maternal transcripts. Particularly, the positive correlation between transcriptional activity and promoter H3K4me3 during EGA was restrained when knocking down of KDM5A, KDM5B and KDM5C. Overall, our work initiatively mapped the genomic reprogramming of H3K4me3 during bovine preimplantation development, and KDM5A/B/C played roles in modulating oocyte-to-embryonic transition (OET) through timely erasure of broad H3K4me3 domains far away from promoters.
2022-03-31 | GSE189101 | GEO
Project description:Reprogramming of histone modification regulates gene expression and mammal preimplantation development. Trimethylation of lysine 4 on histone 3 (H3K4me3) has unique landscape in mouse oocytes and early embryos. However, the dynamics and function of H3K4me3 in livestock embryos remain unclear. To address how it is reprogrammed in domestic animals, we profiled changes of H3K4me3 during bovine early embryo development. Notably, the overall signal of H3K4me3 decreased during embryonic genome activation (EGA). By utilizing ultra-low-input native ChIP-seq (ULI-NChIP-seq) technology, we observed widespread broad H3K4me3 domains in oocytes and embryos. The signal of broad H3K4me3 began to decrease after fertilization and was lowest after EGA. Along with the removal of broad H3K4me3, deposition of H3K4me3 at promoter regions enhanced gradually. Besides, the transcriptional activity and signal of promoter H3K4me3 showed positive correlation after the erasure of broad H3K4me3 at 16-cell stage. Moreover, knocking down of demethylases KDM5A, KDM5B and KDM5C caused EGA delay and blastocyst formation failure. RNA-seq analysis revealed 47.8% down-regulated genes in knockdown embryos at 8/16-cell stage were EGA genes, and 63.1% of up-regulated genes were maternal transcripts. Particularly, the positive correlation between transcriptional activity and promoter H3K4me3 during EGA was restrained when knocking down of KDM5A, KDM5B and KDM5C. Overall, our work initiatively mapped the genomic reprogramming of H3K4me3 during bovine preimplantation development, and KDM5A/B/C played roles in modulating oocyte-to-embryonic transition (OET) through timely erasure of broad H3K4me3 domains far away from promoters.
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2020-05-21 | GSE123815 | GEO
Project description:During maternal-to-embryonic transition control of embryonic development gradually switches from maternal RNAs and proteins stored in the oocyte to gene products generated after embryonic genome activation (EGA). Detailed insight into the onset of embryonic transcription is obscured by the presence of maternal transcripts. Using the bovine model system, we established by RNA sequencing a comprehensive catalogue of transcripts in germinal vesicle and metaphase II oocytes, and in embryos at the 4-cell, 8-cell, 16-cell and blastocyst stages. These were produced by in vitro fertilization of Bos t. taurus oocytes with sperm from a Bos t. indicus bull to facilitate parent-specific transcriptome analysis. Transcripts from 12.4 to 13.7 × 10^3 different genes were detected in the various developmental stages. EGA was analyzed by i) detection of embryonic transcripts which are not present in oocytes; ii) detection of transcripts from the paternal allele; and iii) detection of primary transcripts with intronic sequences. These strategies revealed (i) 220, (ii) 937, and (iii) 6,848 genes to be activated from the 4-cell to the blastocyst stage. The largest proportion of gene activation, i.e. (i) 59%, (ii) 42%, and (iii) 58%, was found in 8-cell embryos, indicating major EGA at this stage. Gene ontology analysis of genes activated at the 4-cell stage identified categories related to translation, RNA processing and transport, consistent with preparation for major EGA. Our study provides the largest transcriptome data set of bovine oocyte maturation and early embryonic development and new insight into the timing of embryonic activation of specific genes.
2014-02-09 | GSE52415 | GEO
Project description:Organisation EGAO00000000260
| EGAO00000000260 | EGA