Peter Askjaer

Peter Askjaer
Andalusian Center for Developmental Biology | CABD

PhD

About

95
Publications
11,373
Reads
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3,659
Citations
Citations since 2017
31 Research Items
1579 Citations
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2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
Additional affiliations
February 2007 - July 2008
Universidad Pablo de Olavide
Position
  • Group Leader
February 2007 - present
Andalusian Center for Developmental Biology
Position
  • Group Leader

Publications

Publications (95)
Preprint
Full-text available
Heterochromatin is characterized by an enrichment of repetitive elements and low gene density and is often maintained in a repressed state across cell division and differentiation. The silencing is mainly regulated by repressive histone marks, such as H3K9 and H3K27 methylated forms and the heterochromatin protein 1 (HP1) family. Here, we analyzed...
Chapter
Development from embryo to adult, organismal homeostasis and ageing are consecutive processes that rely on several functions of the nuclear envelope (NE). The NE compartmentalises the eukaryotic cells and provides physical stability to the genetic material in the nucleus. It provides spatiotemporal regulation of gene expression by controlling nucle...
Article
Full-text available
Control of gene expression in specific tissues and/or at certain stages of development allows the study and manipulation of gene function with high precision. Site-specific genome recombination by the Flippase (FLP) and Cre enzymes has proven particularly relevant. Joint efforts of many research groups have led to the creation of efficient FLP and...
Preprint
Full-text available
Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Here, we report the first whole genome, multiparametric CRISPR anti-aging screen, identifying 43 new genes that can reverse multiple aging phenotypes in progeria. The screen was implemented in fibroblasts from Néstor- Guillermo Progeria Syndro...
Chapter
Nuclear pore complexes (NPCs) are essential to communication of macromolecules between the cell nucleus and the surrounding cytoplasm. RNA synthesized in the nucleus is exported through NPCs to function in the cytoplasm, whereas transcription factors and other proteins are selectively and actively imported. In addition, many NPC constituents, known...
Preprint
Full-text available
Control of gene expression in specific tissues and/or at certain stages of development allows the study and manipulation of gene function with high precision. Site-specific genome recombination by the Flippase (FLP) and Cre enzymes has proven particularly relevant. Joint efforts of many research groups have led to the creation of efficient FLP and...
Article
Transcription is an essential process of DNA metabolism, yet it makes DNA more susceptible to DNA damage. THSC/TREX-2 is a conserved eukaryotic protein complex with a key role in mRNP biogenesis and maturation that prevents genome instability. One source of such instability is linked to transcription as shown in yeast and human cells, but the under...
Article
The spatial organization of chromosomes inside the eukaryotic nucleus is important for DNA replication, repair and gene expression. During development of multicellular organisms, different compendiums of genes are either repressed or activated to produce specific cell types. Genetic manipulation of tractable organisms is invaluable to elucidate chr...
Article
Full-text available
Transcription factors govern many of the time-and tissue-specific gene expression events in living organisms. CEH-60, a homolog of the TALE transcription factor PBX in vertebrates, was recently characterized as a new regulator of intestinal lipid mobilization in Caenorhabdi-tis elegans. Because CEH-60's orthologs and paralogs exhibit several other...
Article
Full-text available
Mutations in the nuclear structural protein lamin A produce rare, tissue-specific diseases called laminopathies. The introduction of a human Emery-Dreifuss muscular dystrophy (EDMD)-inducing mutation into the C. elegans lamin (LMN-Y59C), recapitulates many muscular dystrophy phenotypes, and correlates with hyper-sequestration of a heterochromatic a...
Article
Full-text available
The onset of sexual maturity involves dramatic changes in physiology and gene expression in many animals. These include abundant yolk protein production in egg-laying species, an energetically costly process under extensive transcriptional control. Here, we used the model organism Caenorhabditis elegans to provide evidence for the spatiotemporally...
Article
Full-text available
The eukaryotic nucleus controls most cellular processes. It is isolated from the cytoplasm by the nuclear envelope, which plays a prominent role in the structural organization of the cell, including nucleocytoplasmic communication, chromatin positioning, and gene expression. Alterations in nuclear composition and function are eminently pronounced u...
Article
Full-text available
The execution of developmental programs of gene expression requires an accurate partitioning of the genome into subnuclear compartments, with active euchromatin enriched centrally and silent heterochromatin at the nuclear periphery¹. The existence of degenerative diseases linked to lamin A mutations suggests that perinuclear binding of chromatin co...
Article
Full-text available
In the presence of aggregation-prone proteins, the cytosol and endoplasmic reticulum (ER) undergo a dramatic shift in their respective redox status, with the cytosol becoming more oxidized and the ER more reducing. However, whether and how changes in the cellular redox status may affect protein aggregation is unknown. Here, we show that C. elegans...
Article
Full-text available
Background: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes...
Chapter
The nuclear pore complex (NPC) serves as gateway for transport between the cytoplasm and the nucleus and its structure as well as individual components (nucleoporins or nups) are conserved among all eukaryotes, suggesting they evolved in an ancient common ancestor. In addition to their role in nucleocytoplasmic transport, nups located either at NPC...
Preprint
Full-text available
Background The advancement in automated image based microscopy platforms coupled with high throughput liquid workflows has facilitated the design of large scale screens utilizing multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential g...
Article
Full-text available
Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre and FLP enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans but their use in this nematode is still only sporadic. To i...
Preprint
Full-text available
Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre and FLP enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans but their use in this nematode is still only sporadic. To i...
Article
Full-text available
Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fe...
Article
Full-text available
Author Most animal cells have a nucleus that contains the genetic material: the chromosomes. The nucleus is enclosed by the nuclear envelope, which provides a physical barrier between the chromosomes and the surrounding cytoplasm, and enables precisely controlled transport of proteins into and out of the nucleus. Transport occurs through nuclear p...
Data
MEL-28 is ubiquitously expressed. (A) Embryos were fixed and analyzed with antibodies against MEL-28 and Hoechst to stain DNA (green and magenta in merge, respectively). Single confocal mid sections and maximum projections indicate that MEL-28 is uniformly expressed in all embryonic cells. Approximate developmental time is indicated from fertilizat...
Data
Analysis of MEL-28 expression levels. (A) Compared to a strain that expresses GFP::MEL-28 from the endogenous mel-28 locus after CRISPR/Cas9-mediated GFP knock-in (top panel), expression of GFP::MEL-28 full-length and mutant proteins from transgenes inserted by microparticle bombardment or MosSCI is either similar or lower, thus arguing against the...
Data
Impaired nuclear import and NPC localization of MEL-281-956_loop2mut. (A) Confocal images of embryos expressing GFP::MEL-28 or MEL-281-956_loop2m::GFP. Both embryos also expressed endogenous untagged MEL-28. Scale bars, 5 μm. (B) In interphase, the ratio of nucleoplasmic versus cytoplasmic GFP signal was ~4.4-fold higher for full-length MEL-28 comp...
Data
Analysis of additional MEL-28 fragments. (A) Cropped images from embryos expressing different MEL-28 truncations fused to GFP. Except GFP::MEL-28 all embryos also expressed untagged endogenous MEL-28. (B) MEL-28 truncations for which several transgenic lines were obtained but without showing GFP expression, potentially reflecting reduced mRNA or pr...
Data
Full-length ELYS, but not ELYS fragments, strongly accumulates at kinetochores at mitosis. Cells expressing full-length or truncated GFP-ELYS (green in merge) were analyzed by immunofluorescence with a specific antibody against kinetochore protein CENP-A (red in merge) and DAPI (blue in merge). Single confocal sections (A) and maximum projection im...
Data
The C-terminal domain of ELYS is required for efficient targeting to the nuclear envelope. Fluorescence intensity of the NE and cytoplasm was determined for HeLa cells transiently expressing GFP fused to full-length ELYS (ELYS1-2275), ELYS1-1101, or ELYS1-1700. The ratio of NE versus cytoplasmic fluorescence was reduced by 70–71% for the two trunca...
Data
Maturing C. elegans oocytes expressing GFP::MEL-28 (green) and mCherry::HIS-58 (magenta) observed by confocal microscopy. Time is indicated relative to germinal vesicle breakdown. The video is a merge of two separate recordings: Frames -30 min to 2 min correspond to Fig 1A whereas frames 4 min to 44 min correspond to Fig 1B. Playback speed is 360-7...
Data
Fertilized C. elegans oocytes expressing GFP::TBB-2 (green) and mCherry::HIS-58 (magenta) observed by confocal microscopy. Time is indicated relative to germinal vesicle breakdown. Corresponds to heterozygous mel-28/+ (top) and homozygous mel-28 (bottom) mutants in Fig 1C. Playback speed is 360x. (AVI)
Data
Recording of gastrulating C. elegans embryos to evaluate MEL-28 chromatin binding domain. In the top, control embryo expressing GFP::MEL-28 and in the bottom, embryo expressing GFP::MEL-28Δ1239–1728 observed by confocal microscopy. Red and yellow arrowheads indicate examples of dividing cells. GFP::MEL-28 is associated with kinetochores and chromat...
Data
Recording of gastrulating C. elegans embryos to evaluate minimal MEL-28 chromatin binding domain. Embryos expressing GFP::MEL-28846-1350 (top) or GFP::MEL-28846-1601 (bottom) observed by confocal microscopy. Corresponds to Fig 5. Playback speed is 60x. Frames were taken every 4.6 seconds for 6 minutes. (AVI)
Data
Recording of early C. elegans embryos to evaluate MEL-28 AT-hook domain. Heterozygous (top) and homozygous (bottom) mel-28 embryos expressing GFP::MEL-281-1629 observed by confocal microscopy. Corresponds to Fig 6A. Playback speed is 60x. Frames were taken every 3 seconds for 32 minutes. (AVI)
Data
Recording of early C. elegans embryo to evaluate last MEL-28 AT-hook motif. Embryo expressing GFP::MEL-281-1744 observed by confocal microscopy. Corresponds to Fig 5. Playback speed is 60x. Frames were taken every 4.6 seconds for 34 minutes. (AVI)
Data
Early C. elegans embryo expressing GFP::MEL-28 observed by confocal microscopy. Corresponds to Fig 6A. Playback speed is 60x. Frames were taken every 3 seconds for 32 minutes. (AVI)
Data
Recording of early C. elegans embryos to evaluate MEL-28 coiled-coil domain. In the top, control embryo expressing GFP::MEL-28 and in the bottom, embryo expressing GFP::MEL-28Δ1140–1186 both observed by confocal microscopy. Corresponds to Fig 2C. Playback speed is 60x. Frames were taken every 3 seconds for 24 minutes. (AVI)
Data
Recording of early C. elegans embryos to evaluate MEL-28 loop2 region. Heterozygous (top) and homozygous (bottom) mel-28 embryos expressing MEL-28loop2mut::GFP observed by confocal microscopy. Corresponds to Fig 3A. Playback speed is 60x. Stacks of 7 focal planes were acquired every 15 seconds for 35 minutes; videos represent maximum projection ima...
Data
Recording of early C. elegans embryos to evaluate N-terminal vs. full-length MEL-28. Embryos expressing full-length MEL-28loop2mut::GFP (top) or MEL-281-956_l2m::GFP (bottom) observed by confocal microscopy. Corresponds to Fig 5. Playback speed is 60x. Frames were taken every 6.6 and 4.6 seconds, respectively, for 3 minutes. (AVI)
Article
Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellu...
Article
Full-text available
The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, three-dimensional organizat...
Chapter
The development of genomics and next generation sequencing platforms has dramatically improved our insight into chromatin structure and organization and its fine interplay with gene expression. The nuclear envelope has emerged as a key component in nuclear organization via extensive contacts between the genome and numerous proteins at the nuclear p...
Article
Full-text available
Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green flu...
Article
Protein kinases regulate a multitude of processes by reversible phosphorylation of target molecules. Induction of cell proliferation and differentiation are fundamental to development and rely on tightly controlled kinase activities. Vaccinia-Related Kinases (VRKs) have emerged as a multifunctional family of kinases with essential functions conserv...
Article
Full-text available
SWI/SNF ATP-dependent chromatin remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability and DNA repair. The C. elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.2 encode accessory subunits of SWI/SNF complexes. Using RNAi assays and diverse alleles we investiga...
Chapter
The nuclear lamina, composed of lamins and numerous lamin-associated proteins, is required for mechanical stability, mechanosensing, chromatin organization, developmental gene regulation, mRNA transcription, DNA replication, nuclear assembly, and nuclear positioning. Mutations in lamins or lamin-binding proteins cause at least 18 distinct human dis...
Article
Full-text available
During mitotis, chromosomes are connected to a microtubule-based spindle. Current models propose that displacement of the spindle poles and/or the activity of kinetochore microtubules generate mechanical forces that segregate sister chromatids. Using laser destruction of the centrosomes during C. elegans mitosis, we show that neither of these mecha...
Article
The inner nuclear membrane proteins emerin and LEMD2 have both overlapping and separate functions in regulation of nuclear organization, gene expression and cell differentiation. We report here that emerin/EMR-1 and LEMD2/LEM-2 are expressed in all tissues throughout Caenorhaditis elegans development but their relative distribution differs between...
Article
Full-text available
The adjustment of X-linked gene expression to the X chromosome copy number (dosage compensation [DC]) has been widely studied as a model of chromosome-wide gene regulation. In Caenorhabditis elegans, DC is achieved by twofold down-regulation of gene expression from both Xs in hermaphrodites. We show that in males, the single X chromosome interacts...
Article
The nematode Caenorhabditis elegans is characterized by many features that make it highly attractive to study nuclear pore complexes (NPCs) and nucleocytoplasmic transport. NPC composition and structure are highly conserved in nematodes and being amenable to a variety of genetic manipulations, key aspects of nuclear envelope dynamics can be observe...
Article
Full-text available
In recent years, Caenorhabditis elegans has emerged as a new model to investigate the relationships between nuclear architecture, cellular differentiation, and organismal development. On one hand, C. elegans with its fixed lineage and transparent body is a great model organism to observe gene functions in vivo in specific cell types using microscop...
Article
Nuclear envelope (NE) architecture and aging have been associated since the discovery that certain human progeria diseases are due to perturbations in processing of lamin A protein, generating alterations in NE morphology. However, whether changes in the NE are a causal effect of normal and premature aging is still controversial. Caenorhabditis ele...
Article
Full-text available
Laminopathies are diseases characterized by defects in nuclear envelope structure. A well-known example is Emery-Dreifuss muscular dystrophy, which is caused by mutations in the human lamin A/C and emerin genes. While most nuclear envelope proteins are ubiquitously expressed, laminopathies often affect only a subset of tissues. The molecular mechan...
Article
Full-text available
The precise developmental map of the Caenorhabditis elegans cell lineage, as well as a complete genome sequence and feasibility of genetic manipulation make this nematode species highly attractive to study the role of epigenetics during development. Genetic dissection of phenotypical traits, such as formation of egg-laying organs or starvation-resi...
Article
The factors that sequester transcriptionally repressed heterochromatin at the nuclear periphery are currently unknown. In a genome-wide RNAi screen, we found that depletion of S-adenosylmethionine (SAM) synthetase reduces histone methylation globally and causes derepression and release of heterochromatin from the nuclear periphery in Caenorhabditis...
Article
Full-text available
The Nuclear Pore Complex (NPC) is a fascinating structure whose functional relevance and complexity attract significant interest. Within the NPC, several different subcomplexes interact with each other to form a highly conserved and stable structure. One of these subcomplexes is the NUP107 complex, constituted by 7-9 members. A wide variety of func...
Article
The Nuclear Pore Complex (NPC) is a fascinating structure whose functional relevance and complexity attract significant interest. Within the NPC, several different subcomplexes interact with each other to form a highly conserved and stable structure. One of these subcomplexes is the NUP107 complex, constituted by 7-9 members. A wide variety of func...
Article
Full-text available
Regulation of mitosis in time and space is critical for proper cell division. We conducted an RNA interference-based modifier screen to identify novel regulators of mitosis in Caenorhabditis elegans embryos. Of particular interest, this screen revealed that the Nup205 nucleoporin NPP-3 can negatively modulate the timing of mitotic onset. Furthermor...
Article
Full-text available
Nuclear pore complexes consist of several subcomplexes. The NUP107 complex is important for nucleocytoplasmic transport, nuclear envelope assembly, and kinetochore function. However, the underlying molecular mechanisms and the roles of individual complex members remain elusive. We report the first description of a genetic disruption of NUP107 in a...
Article
The vaccinia-related kinases (VRKs) are highly conserved throughout the animal kingdom and phosphorylate several chromatin proteins and transcription factors. In early Caenorhabditis elegans embryos, VRK-1 is required for proper nuclear envelope formation. In this work, we present the first investigation of the developmental role of VRKs by means o...
Article
The vaccinia-related kinases (VRKs) branched off early from the family of casein kinase (CK) I and compose a relatively uncharacterized family of the kinome. The VRKs were discovered due to their close sequence relation to the vaccinia virus B1R serine/threonine kinase. They were first described in phosphorylation of transcription factors that led...
Article
Nuclear pore complexes (NPCs) are gateways for transport between the nucleus and cytoplasm of eukaryotic cells and play crucial roles in regulation of gene expression. NPCs are composed of multiple copies of approximately 30 different nucleoporins (nups) that display both ubiquitous and cell type specific functions during development. Vertebrate Nu...
Article
Full-text available
The metazoan nuclear envelope (NE) breaks down and re-forms during each cell cycle. Nuclear pore complexes (NPCs), which allow nucleocytoplasmic transport during interphase, assemble into the re-forming NE at the end of mitosis. Using in vitro NE assembly, we show that the vertebrate homologue of MEL-28 (maternal effect lethal), a recently discover...