The Cici Lab develops state-of-the-art geospatial technologies to address real world problems. Our solutions incorporate emerging techniques and theories in Cyberinfrastructure, geospatial analytics, Big Data, machine learning, ontology and semantics, spatial pattern analysis, and scientific visualization. https://www.cici4d-gacor.com/ involve various types of data including geographic, environmental, socioeconomic, political, and other scientific data. The lab collaborates closely with partners in academia, government agencies, industry and nonprofit organizations.

Chromosomal interactions mediated by the CICI complex play important roles in diverse nuclear processes, including DNA replication, repair, and transcription regulation1-5. Chromosome conformation capture methods (Hi-C) have discovered numerous inter- and intra-chromosomal interactions6,7, but understanding their functions remains challenging. One hypothesis is that long-distance chromosomal interactions are required for proper replication timing.8 However, current methods to selectively manipulate specific long-distance chromatomic interactions are limited.

We have developed a biosensor-based method to visualize CICI formation by tracking the distance between pairs of green and red dots in individual cells at high resolution (Methods). This approach allows us to directly monitor the dynamics of CICI formation as a function of time, which is essential to understand its influence on replication timing. We show that the frequency of interaction between a pair of loci correlates strongly with the initial mean distance between them and their initial co-localization probability, CICI efficiency (net co-localization gains at steady state), and the half-time of their formation (Supplementary Fig. 2D-G). Furthermore, a significant proportion of CICI disruption events occur just before cell division (Fig. 1C).

To determine if the observed correlation between CICI frequency and cellular processes is causal, we measured the replication timing of a pair of ARS-RT loci in a control strain expressing a chromosome-specific histone mark (Myo1-mCherry), which forms a ring at the budneck during S phase and disappears upon cell division. We found that whereas the overall average ARS copy number in CICI and non-CICI cells is similar (Fig. 3B), the replication timings of ARS416 and ARS423, which are adjacent to the CICI-forming loci in this strain, differ significantly between the two strains (p values 0.05; two-sided Student's t-test; see Methods).

We conclude that CICI affects replication timing by perturbing the chromosomal interaction network around a pair of replication origins, thereby altering the donor preference during homology-directed DNA repair9. The observed difference is consistent with a model in which long-distance chromatomic interaction networks provide constraints on the spatial location of replication origins. This suggests that the CICI complex is a crucial regulator of the spatiotemporal coordination between chromosomes during cell growth, replication, and cell division.


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Last-modified: 2023-10-16 (月) 00:21:14 (207d)