Reorganization of the interchromosomal network during keratinocyte differentiation.
The well-established human epidermal keratinocyte (HEK) differentiation model was investigated to determine possible alterations in chromosome territory (CT) association during differentiation. The seven human chromosomes (1, 4, 11, 12, 16, 17, and 18) selected for this analysis are representative of the chromosome size and gene density range of the overall human genome as well as including a majority of genes involved in epidermal development and differentiation (CT1, 12, and 17). Induction with calcium chloride (Ca(2+)) resulted in morphological changes characteristic of keratinocyte differentiation. Combined multi-fluorescence in situ hybridization (FISH) and computational image analysis on the undifferentiated (0 h) and differentiated (24 h after Ca(2+) treatment) HEK revealed that (a) increases in CT volumes correspond to overall nuclear volume increases, (b) radial positioning is gene density-dependent at 0 h but neither gene density- nor size-dependent at 24 h, (c) the average number of interchromosomal associations for each CT is gene density-dependent and similar at both time points, and (d) there are striking differences in the single and multiple pairwise interchromosomal association profiles. Probabilistic network models of the overall interchromosomal associations demonstrate major reorganization of the network during differentiation. Only ~40 % of the CT pairwise connections in the networks are common to both 0 and 24 h HEK. We propose that there is a probabilistic chromosome positional code which can be significantly altered during cell differentiation in coordination with reprogramming of gene expression.
Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Nitasha
N
Sehgal
Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Brandon
B
Seifert
Department of Computer Science and Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Hu
H
Ding
Department of Computer Science and Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Zihe
Z
Chen
Department of Computer Science and Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Branislav
B
Stojkovic
Department of Mathematics and Computer Sciences, Fayetteville State University, Fayetteville, NC, 28301, USA.
Sambit
S
Bhattacharya
Department of Computer Science and Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Jinhui
J
Xu
Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA. berezney@buffalo.edu.
Ronald
R
Berezney
D002454:Cell Differentiation / Q000502:physiology*; D002877:Chromosomes, Human / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological
3D FISH; Chromosome territories; Computational image analysis; Interchromosomal networks (ICNs); Keratinocyte differentiation