A5036613537- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Hippo pathway signaling and YAP/TAZ
- Animal Genetics and Reproduction
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cancer-related gene regulation
- T-cell and Retrovirus Studies
- Genetics and Neurodevelopmental Disorders
- Nuclear Structure and Function
- Neurobiology and Insect Physiology Research
- Long-Term Effects of COVID-19
- Cellular transport and secretion
- Signaling Pathways in Disease
- PI3K/AKT/mTOR signaling in cancer
- Plant Molecular Biology Research
- Digital Transformation in Law
- Chromosomal and Genetic Variations
University of South Bohemia in České Budějovice
2013-2024
Sewanee: The University of the South
2011-2019
Google (United States)
2017
Institute of Entomology
2013-2016
Czech Academy of Sciences, Biology Centre
2013-2016
Czech Academy of Sciences
2016
Wellcome Sanger Institute
2006-2010
The Gurdon Institute
2009-2010
University of Cambridge
2009-2010
Wellcome Trust
2004-2009
The completion of whole genome sequencing projects has provided the genetic instructions life. However, whereas identification gene coding regions progressed, mapping transcriptional regulatory motifs moved more slowly. To understand how distinct expression profiles can be established and maintained, a greater understanding these sequences their trans-acting factors is required. Herein we have used combined in silico biochemical approach to identify binding sites [repressor element...
We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), H4 5/8/12/16 (H4ac), and at 4 mono-, di-, trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including Consortium common GM06990 (lymphoblastoid) HeLa-S3, as well K562, HFL-1, MOLT4, we identified clear patterns profiles with respect to genomic features. H3ac modifications are tightly associated transcriptional start sites (TSSs)...
Significance Here we reassess the conceptual framework of insect diapause as a dynamic succession endogenously and exogenously driven changes in physiology (“physiogenesis”) by assaying gradual dynamics transcriptome insects traverse developmental program. We show objectivity eco-physiological relevance different phases development describing unique transcriptional profiles each phase. Accordingly, concept should serve future researchers general platform for unification timing scales...
The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It over 2.47 million deaths through various syndromes such as distress, hypercoagulability, and multiple organ failure. viral invasion proceeds the ACE2 receptor, expressed in cell types, some patients serious damage to tissues, organs, immune cells, microbes that colonize gastrointestinal tract (GIT). Some who...
Abstract Histone H3 methylation at R17 and R26 recently emerged as a novel epigenetic mechanism regulating pluripotency in mouse embryos. Blastomeres of four-cell embryos with high these sites show unrestricted potential, whereas those lower levels cannot support development when aggregated chimeras like cells. Increasing histone methylation, through expression coactivator-associated-protein-arginine-methyltransferase 1 (CARM1) embryos, elevates key genes directs cells to the pluripotent...
Abstract Successful specification of the two mouse blastocyst inner cell mass (ICM) lineages (the primitive endoderm (PrE) and epiblast) is a prerequisite for continued development requires active fibroblast growth factor 4 (FGF4) signaling. Previously, we identified role p38 mitogen-activated protein kinases (p38-MAPKs) during PrE differentiation, but underlying mechanisms have remained unresolved. Here, report an early window p38-MAPK activity that required to regulate ribosome-related...
Divisions of polarised blastomeres that allocate polar cells to outer and apolar inner positions initiate the first cell fate decision in mouse embryo. Subsequently, differentiate into trophectoderm while retain pluripotency become mass (ICM) blastocyst. Elimination zygotic expression trophectoderm-specific transcription factor Cdx2 leads defects maintenance blastocyst cavity, suggesting it participates only late stage formation. However, we now find embryos also have a maternally provided...
The molecular events that contribute to, and result from, the in vivo binding of transcription factors to their cognate DNA sequence motifs mammalian genomes are poorly understood. We demonstrate variations within bind transcriptional repressor REST (NRSF) encode affinity hierarchies regulatory function during lineage-specific developmental programs fundamental ways. First, canonical for facilitate strong control functional classes targets common all cell types, whilst atypical participate...
It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons ("exon-intron marking"), linking chromatin structure function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across human genome three cell types, we have found this system is far more...
Abstract During mouse preimplantation embryo development, three distinct cell lineages are formed, represented by the differentiating trophectoderm (TE), primitive endoderm (PrE) and pluripotent epiblast (EPI). Classically, lineage derivation has been presented as a two-step process whereby outer TE cells first segregated from inner-cell mass (ICM), followed ICM refinement into either PrE or EPI. As founders can be produced following fourth fifth cleavage divisions, their potential to...
Establishment of neuronal identity requires co-ordinated expression specific batteries genes. These programs gene are executed by activation neuron-specific genes in cells and their repression non-neuronal cells. Such co-ordinate regulation that individual activators repressors regulate transcription from subsets potential target genes, yet we know little the mechanisms underlie this selective process. The RE-1 silencing factor (REST) is a repressor proposed to silence numerous via...
Translation is critical for development as transcription in the oocyte and early embryo silenced. To illustrate translational changes during meiosis consecutive two mitoses of embryo, we performed a genome-wide translatome analysis. Acquired data showed significant uniform activation key initiation elongation axes specific to M-phases. Although global protein synthesis decreases M-phases, translation activity increases uniformly fluctuating manner, leading qualitative regulation via...
During mouse preimplantation embryo development, the classically described second cell-fate decision involves specification and segregation, in blastocyst inner cell mass (ICM), of primitive endoderm (PrE) from pluripotent epiblast (EPI). The active role fibroblast growth factor (Fgf) signalling during PrE differentiation, particularly context Erk1/2 pathway activation, is well described. However, we report that p38 family mitogen-activated protein kinases (namely p38α/Mapk14 p38β/Mapk11;...
Meiotic maturation of oocyte relies on pre-synthesised maternal mRNA, the translation which is highly coordinated in space and time. Here, we provide a detailed polysome profiling protocol that demonstrates combination sucrose gradient ultracentrifugation small SW55Ti tubes with qRT-PCR-based quantification 18S 28S rRNAs fractionated profile. This newly optimised method, named Scarce Sample Polysome Profiling (SSP-profiling), suitable for both scarce conventional sample sizes compatible...
Abstract Release of distinct cellular cargoes in response to specific stimuli is a process fundamental all higher eukaryotes and controlled by the regulated secretory pathway (RSP). However, mechanism which genes involved RSP are selectively expressed, leading establishment appropriate functioning secretion remaining largely unknown. Using rat pheochromocytoma cell line PC12, we provide evidence that, controlling expression many RSP, transcriptional repressor REST can regulate this hence...
Preimplantation mouse embryo development involves temporal-spatial specification and segregation of three blastocyst cell lineages: trophectoderm, primitive endoderm epiblast. Spatial separation the outer-trophectoderm lineage from two other inner-cell-mass (ICM) lineages starts with 8- to 16-cell transition concludes at 32-cell stages. Accordingly, ICM is derived primary secondary contributed cells; debated relative EPI versus PrE potencies. We report generation but not populations highly...
The rate of chromosome segregation errors that emerge during meiosis I in the mammalian female germ line are known to increase with maternal age; however, little is about underlying molecular mechanism. objective this study was analyze meiotic progression mouse oocytes relation age. Using as a model system, we analyzed timing nuclear envelope breakdown and morphology lamina obtained from young (2 months old) aged females (12 old). Oocytes older display significantly faster through compared...
The identification of cis -regulatory elements is central to understanding gene transcription. Hypersensitivity digestion with DNaseI remains the gold-standard approach locating such elements. Traditional methods used identify hypersensitive sites are cumbersome and can only be applied short stretches DNA at defined locations. Here we report development a novel genomic array-based site mapping (ADHM) that permits precise, large-scale from as few 5 million cells. Using ADHM identified all...
Abstract Increasing maternal age in mammals is associated with poorer oocyte quality, involving higher aneuploidy rates and decreased developmental competence. Prior to resumption of meiosis, fully developed mammalian oocytes become transcriptionally silent until the onset zygotic genome activation. Therefore, meiotic progression early embryogenesis are driven largely by translational utilization previously synthesized mRNAs. We report that genome‐wide translatome profiling reveals...