Biology subjects

Becker, C.

Publications and source records attributed to Becker, C..

5 recordsLinked to original sources

bioRxiv2018

GWAS meta-analysis highlights the hypothalamic-pituitary-gonadal axis (HPG axis) in the genetic regulation of menstrual cycle length

The normal menstrual cycle requires a delicate interplay between the hypothalamus, pituitary, and ovary. Therefore, its length is an important indicator of female reproductive health. Menstrual cycle length has been shown to be partially controlled by genetic factors, especially in the follicle stimulating hormone beta-subunit (FSHB) locus. GWAS meta-analysis of menstrual cycle length in 44,871 women of European ancestry confirmed the previously observed association with the FSHB locus and identified four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2 genes. These findings confirm the role of the hypothalamic-pituitary-gonadal axis in the genetic regulation of menstrual cycle length, but also highlight potential novel local regulatory mechanisms, such as those mediated by IGF2.

genetics↗

bioRxiv2018

Incomplete reprogramming of cell-specific epigenetic marks during asexual reproduction leads to heritable phenotypic variation in plants

Plants differ from animals in their capability to easily regenerate fertile adult individuals from terminally differentiated cells [1]. This unique developmental plasticity is commonly observed in nature where many species can reproduce asexually through the ectopic initiation of organogenic or embryogenic developmental programs [2, 3]. However, it is not currently known if this developmental reprogramming is coupled to a global epigenomic resetting, or what impact it has on the phenotype of the clonal progeny. Here we show that plants asexually propagated via induction of a zygotic developmental program do not fully reset cell-specific epigenetic imprints. These imprints are instead inherited even over multiple rounds of sexual reproduction, becoming fixed in hybrids and resulting in heritable molecular and physiological phenotypes that depend on the founder cell used. Our results demonstrate how novel phenotypic variation in plants can be unlocked through the incomplete reprogramming of cell-specific epigenetic marks during asexual propagation.

plant biology↗

bioRxiv2017

On the difficulty to interpret results when animals are singly housed: experimental epilepsy as a prototypical example

Many experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy. Control male mice socially housed during pretest and then transferred to individual cages for six weeks displayed anhedonia, increased anxiety and biological markers of stress as compared to pretest values or mice kept socially housed during six weeks. Pilocarpine-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group. The differences were more significant in pilocarpine-treated mice housed individually. Anxiety correlated linearly with cognitive performance and stress markers independently of the experimental conditions. In the male rat pilocarpine model, seizures were sixteen times more frequent in singly housed animals as compared to animals kept in pairs. Daily interactions with an experimenter in otherwise singly housed animals was sufficient to produce results identical to those found in animals kept in pairs. We propose that social isolation produces a severe phenotype in terms of stress and seizure frequency as compared to animals maintaining social contact (at least in these two models), a factor that needs to be taken into account for data interpretation, in particular for preclinical studies.\n\nSignificance StatementMany experimental approaches require housing rodents in individual cages, a stressful condition for social animals, even in an enriched environment context. Using the pilocarpine model of epilepsy in rats and mice, we report that singly housing animals develop a more severe phenotype in terms of stress and epilepsy as compared to animals maintaining social contact. We propose that social isolation adds a degree of complexity for the interpretation of data, which may be particularly relevant for preclinical studies.

neuroscience↗

bioRxiv2017

Ecological plant epigenetics: Evidence from model and non-model species, and the way forward

Growing evidence makes a strong case that epigenetic mechanisms contribute to complex traits, with implications across many fields of biology from dissecting developmental processes to understanding aspects of human health and disease. In ecology, recent studies have merged ecological experimental design with epigenetic analyses to elucidate the contribution of epigenetics to plant phenotypes, stress response, adaptation to habitat, or species range distributions. While there has been some progress in revealing the role of epigenetics in ecological processes, many studies with non-model species have so far been limited to describing broad patterns based on anonymous markers of DNA methylation. In contrast, studies with model species have benefited from powerful genomic resources, which allow for a more mechanistic understanding but have limited ecological realism. To understand the true significance of epigenetics for plant ecology and evolution, we must combine both approaches transferring knowledge and methods from model-species research to genomes of evolutionarily divergent species, and examining responses to complex natural environments at a more mechanistic level. This requires transforming genomics tools specifically for studying non-model species, which is challenging given the large and often polyploid genomes of plants. Collaboration between molecular epigeneticists, ecologists and bioinformaticians promises to enhance our understanding of the mutual links between genome function and ecological processes.

ecology↗

bioRxiv2017

Topological Demarcation By HMGB2 Is Disrupted Early Upon Senescence Entry Across Cell Types And Induces CTCF Clustering

Ageing-relevant processes, like cellular senescence, are characterized by complex, often stochastic, events giving rise to heterogeneous cell populations. We hypothesized that entry into senescence of different primary human cells can be triggered by one early molecular event affecting the spatial organization of chromosomes. To test this, we combined whole-genome chromosome conformation capture, population and single-cell transcriptomics, super-resolution imaging, and functional analyses applied on proliferating and replicatively-senescent populations from three distinct human cell types. We found a number of genes involved in DNA conformation maintenance being suppressed upon senescence across cell types. Of these, the abundant high mobility group (HMG) B1 and B2 nuclear factors are quantitatively removed from cell nuclei before typical senescence markers appear, and mark a subset of topologically-associating domain (TAD) boundaries. Their loss coincides with obvious reorganization of chromatin interactions via the dramatic spatial clustering of CTCF foci. HMGB2 knock-down recapitulates this senescence-induced CTCF clustering, while also affecting insulation at TAD boundaries. We accordingly propose that HMGB-mediated deregulation of chromosome conformation constitutes a primer for the ensuing senescent program across cell types.

genomics↗