Dekker J, Alber F, Aufmkolk S, Believeau BJ, Bruneau BG, Belmont AS, Bintu L, Boettiger A, Calandrelli R, Disteche CM, Gilbert DM, Gregor T, Hansen AS, Huang B, Huangfu D, Kalhor R, Leslie CS, Li W, Li Y, Ma J, Noble WS, Park PJ, Phillips-Cremins JE, Pollard KS, Rafelski SM, Ren B, Ruan Y, Shav-Tal Y, Shen Y, Shendure J, Shu X, Strambio-De-Castilla C, Vertii A, Zhang H, Zhong S.
Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project. Molecular Cell 2023;83(15):2624-2640.
AbstractThe four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and
RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between
genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize
cis-determinants and
trans-modulators of
genome organization, (3) test functional consequences of changes in
cis- and
trans-regulators, and (4) develop predictive models of genome structure and function.
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