Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA-bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.DOI: http://dx.doi.org/10.7554/eLife.23326.001
Single-cell analyses in budding yeast reveal that neighboring replicons are assembled stochastically and stay associated to maintain stable replication factories.
Background The second wave of the COVID-19 pandemic led to substantial differences in incidence rates across Germany. Methods Assumption-free k-nearest neighbour clustering from the principal component analysis of weekly incidence rates of German counties groups similar spreading behaviour. Different spreading dynamics was analysed by the derivative plots of the temporal evolution of tuples [x(t),x’(t)] of weekly incidence rates and their derivatives. The effectiveness of the different shutdown measures in Germany during the second wave is assessed by the difference of weekly incidences before and after the respective time periods. Findings The implementation of non-pharmaceutical interventions of different extents resulted in four distinct time periods of complex, spatially diverse, and age-related spreading patterns during the second wave of the COVID-19 pandemic in Germany. Clustering gave three regions of coincident spreading characteristics. October 2020 showed a nationwide exponential growth of weekly incidence rates with a doubling time of 10 days. A partial shutdown during November 2020 decreased the overall infection rates by 20–40% with a plateau-like behaviour in northern and southwestern Germany. The eastern parts exhibited a further near-linear growth by 30–80%. Allover the incidence rates among people above 60 years still increased by 15–35% during partial shutdown measures. Only an extended shutdown led to a substantial decrease in incidence rates. These measures decreased the numbers among all age groups and in all regions by 15–45%. This decline until January 2021 was about -1•25 times the October 2020 growth rates with a strong correlation of -0•96. Interpretation Three regional groups with different dynamics and different degrees of effectiveness of the applied measures were identified. The partial shutdown was moderately effective and at most stopped the exponential growth, but the spread remained partly plateau-like and regionally continued to grow in a nearly linear fashion. Only the extended shutdown reversed the linear growth. Funding Institutional support and physical resources were provided by the University Witten/ Herdecke and Kliniken der Stadt Köln, German ministry of education and research ‘Netzwerk Universitätsmedizin’ (NUM), egePan Unimed (01KX2021).
Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA-bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.
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