scholarly journals Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction

2019 ◽  
Author(s):  
Stefano Gnan ◽  
Ilya M. Flyamer ◽  
Kyle N. Klein ◽  
Eleonora Castelli ◽  
Alexander Rapp ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Nuclear Architecture ◽  
Replication Timing ◽  
Function Approach ◽  
Dual Function ◽  
Genome Organisation ◽  
Full Complement ◽  
Nuclear Organisation ◽  
Molecular Bases

AbstractThree-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing program and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. RIF1’s role in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing program and nuclear architecture.

scholarly journals Nuclear organisation and replication timing are coupled through RIF1–PP1 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stefano Gnan ◽  
Ilya M. Flyamer ◽  
Kyle N. Klein ◽  
Eleonora Castelli ◽  
Alexander Rapp ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Nuclear Architecture ◽  
Replication Timing ◽  
Function Approach ◽  
Dual Function ◽  
Genome Organisation ◽  
Full Complement ◽  
Nuclear Organisation ◽  
Molecular Bases

AbstractThree-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. The role of RIF1 in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing programme and nuclear architecture.

scholarly journals Three-dimensional organization of Drosophila melanogaster interphase nuclei. I. Tissue-specific aspects of polytene nuclear architecture.

1987 ◽  
Vol 104 (6) ◽  
pp. 1455-1470 ◽  
Author(s):  
M Hochstrasser ◽  
J W Sedat
Keyword(s):  
Drosophila Melanogaster ◽  
Three Dimensional ◽  
Nuclear Architecture ◽  
Close Packing ◽  
Prothoracic Gland ◽  
Cell Type ◽  
Interphase Chromosome ◽  
Tissue Specific ◽  
Spatial Domains ◽  
Four Levels

Interphase chromosome organization in four different Drosophila melanogaster tissues, covering three to four levels of polyteny, has been analyzed. The results are based primarily on three-dimensional reconstructions from unfixed tissues using a computer-based data collection and modeling system. A characteristic organization of chromosomes in each cell type is observed, independent of polyteny, with some packing motifs common to several or all tissues and others tissue-specific. All chromosomes display a right-handed coiling chirality, despite large differences in size and degree of coiling. Conversely, in each cell type, the heterochromatic centromeric regions have a unique structure, tendency to associate, and intranuclear location. The organization of condensed nucleolar chromatin is also tissue-specific. The tightly coiled prothoracic gland chromosomes are arrayed in a similar fashion to the much larger salivary gland chromosomes described previously, having polarized orientations, nonintertwined spatial domains, and close packing of the arms of each autosome, whereas hindgut and especially the unusually straight midgut chromosomes display striking departures from these regularities. Surprisingly, gut chromosomes often appear to be broken in the centric heterochromatin. Severe deformations of midgut nuclei observed during gut contractions in living larvae may account for their unusual properties. Finally, morphometric measurements of chromosome and nuclear dimensions provide insights into chromosome growth and substructure and also suggest an unexpected parallel with diploid chromatin organization.

Three-dimensional ionospheric tomography reconstruction using the model function approach in Tikhonov regularization

2016 ◽  
Vol 121 (12) ◽  
pp. 12,104-12,115 ◽  
Author(s):  
Sicheng Wang ◽  
Sixun Huang ◽  
Jie Xiang ◽  
Hanxian Fang ◽  
Jian Feng ◽  
...  
Keyword(s):  
Tikhonov Regularization ◽  
Three Dimensional ◽  
Function Approach ◽  
Model Function ◽  
Ionospheric Tomography ◽  
Tomography Reconstruction

Novel automated three-dimensional genome scanning based on the nuclear architecture of telomeres

2010 ◽  
Vol 79A (2) ◽  
pp. 159-166 ◽  
Author(s):  
Ludger Klewes ◽  
Clemens Höbsch ◽  
Nir Katzir ◽  
David Rourke ◽  
Yuval Garini ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Nuclear Architecture ◽  
Genome Scanning

scholarly journals Analysis of the structural variability of topologically associated domains as revealed by Hi-C

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Natalie Sauerwald ◽  
Akshat Singhal ◽  
Carl Kingsford
Keyword(s):  
Structural Changes ◽  
Chromosome Structure ◽  
Three Dimensional ◽  
Replication Timing ◽  
Building Blocks ◽  
Structural Features ◽  
Genetic Sequence ◽  
Experimental Variation ◽  
Topologically Associated Domains ◽  
Integral Role

Abstract Three-dimensional chromosome structure plays an integral role in gene expression and regulation, replication timing, and other cellular processes. Topologically associated domains (TADs), building blocks of chromosome structure, are genomic regions with higher contact frequencies within the region than outside the region. A central question is the degree to which TADs are conserved or vary between conditions. We analyze 137 Hi-C samples from 9 studies under 3 measures to quantify the effects of various sources of biological and experimental variation. We observe significant variation in TAD sets between both non-replicate and replicate samples, and provide initial evidence that this variability does not come from genetic sequence differences. The effects of experimental protocol differences are also measured, demonstrating that samples can have protocol-specific structural changes, but that TADs are generally robust to lab-specific differences. This study represents a systematic quantification of key factors influencing comparisons of chromosome structure, suggesting significant variability and the potential for cell-type-specific structural features, which has previously not been systematically explored. The lack of observed influence of heredity and genetic differences on chromosome structure suggests that factors other than the genetic sequence are driving this structure, which plays an important role in human disease and cellular functioning.

scholarly journals Cell fate transitions and the replication timing decision point

2010 ◽  
Vol 191 (5) ◽  
pp. 899-903 ◽  
Author(s):  
David M. Gilbert
Keyword(s):  
Cell Fate ◽  
Large Scale ◽  
Three Dimensional ◽  
Replication Timing ◽  
Window Of Opportunity ◽  
Decision Point ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Timing Decision ◽  
3D Architecture

Recent findings suggest that large-scale remodeling of three dimensional (3D) chromatin architecture occurs during a brief period in early G1 phase termed the replication timing decision point (TDP). In this speculative article, I suggest that the TDP may represent an as yet unappreciated window of opportunity for extracellular cues to influence 3D architecture during stem cell fate decisions. I also describe several testable predictions of this hypothesis.

scholarly journals Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program

2016 ◽  
Vol 61 (2) ◽  
pp. 260-273 ◽  
Author(s):  
Rossana Foti ◽  
Stefano Gnan ◽  
Daniela Cornacchia ◽  
Vishnu Dileep ◽  
Aydan Bulut-Karslioglu ◽  
...  
Keyword(s):  
Nuclear Architecture ◽  
Replication Timing

scholarly journals Replication timing maintains the global epigenetic state in human cells

Science ◽  
2021 ◽  
Vol 372 (6540) ◽  
pp. 371-378
Author(s):  
Kyle N. Klein ◽  
Peiyao A. Zhao ◽  
Xiaowen Lyu ◽  
Takayo Sasaki ◽  
Daniel A. Bartlett ◽  
...  
Keyword(s):  
Dna Replication ◽  
Histone Modifications ◽  
Temporal Order ◽  
Three Dimensional ◽  
Replication Timing ◽  
Human Cells ◽  
Genome Architecture ◽  
Chromatin Modifications ◽  
Complete Elimination ◽  
Epigenetic State

The temporal order of DNA replication [replication timing (RT)] is correlated with chromatin modifications and three-dimensional genome architecture; however, causal links have not been established, largely because of an inability to manipulate the global RT program. We show that loss of RIF1 causes near-complete elimination of the RT program by increasing heterogeneity between individual cells. RT changes are coupled with widespread alterations in chromatin modifications and genome compartmentalization. Conditional depletion of RIF1 causes replication-dependent disruption of histone modifications and alterations in genome architecture. These effects were magnified with successive cycles of altered RT. These results support models in which the timing of chromatin replication and thus assembly plays a key role in maintaining the global epigenetic state.

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