Inferring the three-dimensional structures of the X-chromosome during X-inactivation

Hao Zhu, Nan Wang, Jonathan Z. Sun, Ras B. Pandey, Zheng Wang

Research output: Contribution to journalArticle

Abstract

The Hi-C experiment can capture the genome-wide spatial proximities of the DNA, based on which it is possible to computationally reconstruct the three-dimensional (3D) structures of chromosomes. The transcripts of the long non-coding RNA (lncRNA) Xist spread throughout the entire X-chromosome and alter the 3D structure of the X-chromosome, which also inactivates one copy of the two X-chromosomes in a cell. The Hi-C experiments are expensive and time-consuming to conduct, but the Hi-C data of the active and inactive X-chromosomes are available. However, the Hi-C data of the X-chromosome during the process of X-chromosome inactivation (XCI) are not available. Therefore, the 3D structure of the X-chromosome during the process of X-chromosome inactivation (XCI) remains to be unknown. We have developed a new approach to reconstruct the 3D structure of the X-chromosome during XCI, in which the chain of DNA beads representing a chromosome is stored and simulated inside a 3D cubic lattice. A 2D Gaussian function is used to model the zero values in the 2D Hi-C contact matrices. By applying simulated annealing and Metropolis-Hastings simulations, we first generated the 3D structures of the X-chromosome before and after XCI. Then, we used Xist localization intensities on the X-chromosome (RAP data) to model the traveling speeds or acceleration between all bead pairs during the process of XCI. The 3D structures of the X-chromosome at 3 hours, 6 hours, and 24 hours after the start of the Xist expression, which initiates the XCI process, have been reconstructed. The source code and the reconstructed 3D structures of the X-chromosome can be downloaded from http://dna.cs.miami.edu/3D-XCI/.

Original languageEnglish (US)
Pages (from-to)7384-7404
Number of pages21
JournalMathematical Biosciences and Engineering
Volume16
Issue number6
DOIs
StatePublished - Jan 1 2019

Fingerprint

X Chromosome Inactivation
X Chromosome
X chromosome
Chromosomes
Chromosome
inactivation
Three-dimensional
Long Noncoding RNA
Chromosome Structures
Chromosomes, Human, Pair 3
DNA
chromosomes
Metropolis-Hastings
Genome
annealing

Keywords

  • 3D cubic lattice
  • 3D genome
  • LncRNA
  • Simulation
  • X-chromosome inactivation
  • Xist

ASJC Scopus subject areas

  • Modeling and Simulation
  • Agricultural and Biological Sciences(all)
  • Computational Mathematics
  • Applied Mathematics

Cite this

Inferring the three-dimensional structures of the X-chromosome during X-inactivation. / Zhu, Hao; Wang, Nan; Sun, Jonathan Z.; Pandey, Ras B.; Wang, Zheng.

In: Mathematical Biosciences and Engineering, Vol. 16, No. 6, 01.01.2019, p. 7384-7404.

Research output: Contribution to journalArticle

Zhu, Hao ; Wang, Nan ; Sun, Jonathan Z. ; Pandey, Ras B. ; Wang, Zheng. / Inferring the three-dimensional structures of the X-chromosome during X-inactivation. In: Mathematical Biosciences and Engineering. 2019 ; Vol. 16, No. 6. pp. 7384-7404.
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