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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Background: Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programs. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood.
Results: We characterized the relationship of chromatin accessibility, gene expression, and DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated with changes in gene expression, and many of the target genes could be associated with the developmental stage in which they are transcriptionally controlled. We also observe dynamic changes in chromatin accessibility during flower development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely independent of the accessibility status of their binding regions and it can precede increases in DNA accessibility. These results suggest that APETALA1 and SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes.
Conclusions: Our findings indicate that different homeotic factors regulate partly overlapping, yet also distinctive sets of target genes in a partly stage-specific fashion. By combining the information from DNA-binding and gene expression data, we are able to propose models of stage-specific regulatory interactions, thereby addressing dynamics of regulatory networks throughout flower development. Furthermore, MADS-domain TFs may regulate gene expression by alternative strategies, one of which is modulation of chromatin accessibility.
Background: Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programs. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood.
Results: We characterized the relationship of chromatin accessibility, gene expression, and DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated with changes in gene expression, and many of the target genes could be associated with the developmental stage in which they are transcriptionally controlled. We also observe dynamic changes in chromatin accessibility during flower development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely independent of the accessibility status of their binding regions and it can precede increases in DNA accessibility. These results suggest that APETALA1 and SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes.
Conclusions: Our findings indicate that different homeotic factors regulate partly overlapping, yet also distinctive sets of target genes in a partly stage-specific fashion. By combining the information from DNA-binding and gene expression data, we are able to propose models of stage-specific regulatory interactions, thereby addressing dynamics of regulatory networks throughout flower development. Furthermore, MADS-domain TFs may regulate gene expression by alternative strategies, one of which is modulation of chromatin accessibility.
The large variety of atmospheric circulation systems affecting the eastern Asian climate is reflected by the complex Asian vegetation distribution. Particularly in the transition zones of these circulation systems, vegetation is supposed to be very sensitive to climate change. Since proxy records are scarce, hitherto a mechanistic understanding of the past spatio-temporal climate-vegetation relationship is lacking. To assess the Holocene vegetation change and to obtain an ensemble of potential mid-Holocene biome distributions for eastern Asia, we forced the diagnostic biome model BIOME4 with climate anomalies of different transient Holocene climate simulations performed in coupled atmosphere-ocean(-vegetation) models. The simulated biome changes are compared with pollen-based biome records for different key regions.
In all simulations, substantial biome shifts during the last 6000 years are confined to the high northern latitudes and the monsoon-westerly wind transition zone, but the temporal evolution and amplitude of change strongly depend on the climate forcing. Large parts of the southern tundra are replaced by taiga during the mid-Holocene due to a warmer growing season and the boreal treeline in northern Asia is shifted northward by approx. 4 degrees in the ensemble mean, ranging from 1.5 to 6 degrees in the individual simulations, respectively. This simulated treeline shift is in agreement with pollen-based reconstructions from northern Siberia. The desert fraction in the transition zone is reduced by 21% during the mid-Holocene compared to pre-industrial due to enhanced precipitation. The desert-steppe margin is shifted westward by 5 degrees (1-9 degrees in the individual simulations). The forest biomes are expanded north-westward by 2 degrees, ranging from 0 to 4 degrees in the single simulations. These results corroborate pollen-based reconstructions indicating an extended forest area in north-central China during the mid-Holocene. According to the model, the forest-to-non-forest and steppe-to-desert changes in the climate transition zones are spatially not uniform and not linear since the mid-Holocene.
The large variety of atmospheric circulation systems affecting the eastern Asian climate is reflected by the complex Asian vegetation distribution. Particularly in the transition zones of these circulation systems, vegetation is supposed to be very sensitive to climate change. Since proxy records are scarce, hitherto a mechanistic understanding of the past spatio-temporal climate-vegetation relationship is lacking. To assess the Holocene vegetation change and to obtain an ensemble of potential mid-Holocene biome distributions for eastern Asia, we forced the diagnostic biome model BIOME4 with climate anomalies of different transient Holocene climate simulations performed in coupled atmosphere-ocean(-vegetation) models. The simulated biome changes are compared with pollen-based biome records for different key regions. In all simulations, substantial biome shifts during the last 6000 years are confined to the high northern latitudes and the monsoon-westerly wind transition zone, but the temporal evolution and amplitude of change strongly depend on the climate forcing. Large parts of the southern tundra are replaced by taiga during the mid-Holocene due to a warmer growing season and the boreal treeline in northern Asia is shifted northward by approx. 4 degrees in the ensemble mean, ranging from 1.5 to 6 degrees in the individual simulations, respectively. This simulated treeline shift is in agreement with pollen-based reconstructions from northern Siberia. The desert fraction in the transition zone is reduced by 21% during the mid-Holocene compared to pre-industrial due to enhanced precipitation. The desert-steppe margin is shifted westward by 5 degrees (1-9 degrees in the individual simulations). The forest biomes are expanded north-westward by 2 degrees, ranging from 0 to 4 degrees in the single simulations. These results corroborate pollen-based reconstructions indicating an extended forest area in north-central China during the mid-Holocene. According to the model, the forest-to-non-forest and steppe-to-desert changes in the climate transition zones are spatially not uniform and not linear since the mid-Holocene.