Abstract
For studying the 3D structure formed by consecutive genomic regions of chromosomes we propose using statistical shape theory in conjunction with registration methods. In contrast to earlier work, where the 3D chromatin structure was analyzed indirectly, we here directly exploit the 3D locations of genomic regions to determine the large-scale structure of chromatin fiber. Our study is based on 3D microscopy images of the X-chromosome where four consecutive genomic regions (BACs) have been simultaneously labeled by multicolor FISH. To allow unique reconstruction of the 3D shape, image data with sets of four consecutive BACs have been acquired with an overlap of three BACs between the different sets. We have statistically analyzed the data and it turned out that for all datasets the 3D structure is non-random. In addition, we found that the shapes of active and inactive X-chromosomal genomic regions are statistically independent. Moreover, we reconstructed the 3D structure of chromatin in a small genomic region based on five BACs resulting from two overlapping four BACs. We also found that spatial normalization of cell nuclei using non-rigid image registration has a significant influence on the location of the genomic regions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adams DC, Rohlf FJ, Slice DE (2004) Geometric morphometrics: ten years of progress following the ‘revolution’. Ital J Zool 71:5–16
Chikuse Y, Jupp PE (2004) A test of uniformity on shape spaces. J Multivar Anal 88:163–176
Chuang C, Belmont A (2007) Moving chromatin within the interphase nucleus-controlled transitions? Semin Cell Dev Biol 18:698–706
Chuang C, Carpenter A, Fuchsova B, Johnson T, de Lanerole P, Belmont AS (2006) Long-range directional movement of an interphase chromosome site. Curr Biol 16:825–831
Cremer M, von Hase J, Volm T, Brero A, Kreth G, Walter J, Fischer C, Solovei I, Cremer C, Cremer T (2001) Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells. Chromo Res 9(7):541–567
Cremer M, Müller S, Köhler D, Brero A, Solovei I (2007) Cell preparation and multicolor FISH in 3D preserved cultured mammalian cells, CSH Protocols, doi:10.1101/pdb.prot4723
Dryden I, Mardia K (1998) Statistical Shape Analysis. Wiley, Chichester
Dundr M, Ospina J, Sung M, John S, Upender M, Ried T, Hager G, Matera A (2007) Actin-dependent intranuclear repositioning of an active gene locus in vivo. J Cell Biol 179:1095–1103
Fisher NI, Lewis T, Embleton B (1987) Statistical analysis of spherical data. The Press Syndicate of the University of Cambridge, Cambridge
Fraser P, Bickmore W (2007) Nuclear organization of the genome and the potential for gene regulation. Nature 447:413–417
Götze S, Mateos-Langerak J, Gierman HJ, de Leeuw W, Giromus O, Indemans MHG, Koster J, Ondrej V, Versteeg R, van Driel R (2007) The three-dimensional structure of human interphase chromosomes is related to the transcriptome map. Mol Cell Biol 27(12):4475–4487
Horn B (1987) Closed-form solution of absolute orientation using unit quaternions. J Opt Soc Am A 4:629–642
Ibanez L, Schroeder W, Ng L, Cates J (2005) The ITK software guide. Kitware, New York
Jupp PE, Mardia KV (1980) A general correlation coefficient for directional data and related regression problems. Biometrika 67(1):163–173
Kosak S, Groudine M (2004) Form follows function: the genomic organization of cellular differentiation. Genes Dev 18:1371–1384
Kozubek S, Lukásová E, Jirsová P, Koutná I, Kozubek M, Ganová A, Bártová E, Falk M, Paseková R (2002) 3D structure of the human genome: order in randomness. Chromosoma 111:321–331
Lanctôt C, Cheutin T, Cremer M, Cavalli G, Cremer T (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 8(2):104–115
Lyon M (1961) Gene action in the x-chromosome of the mouse (mus musculus l.). Nature 190:372–373
Mardia KV, Jupp PE (2000) Directional statistics. Wiley, Chichester
Ostashevsky J (1998) A polymer model for the structural organization of chromatin loops and minibands in interphase chromosomes. Mol Biol Cell 9:3031–3040
Parreira L, Telhada M, Ramos C, Hernandez R, Neves H, Carmo-Fonseca M (1997) The spatial distribution of human immunoglobulin genes within the nucleus: evidence for gene topography independent of cell type and transcriptional activity. Hum Genet 100:588–594
Ragoczy T, Bender M, Telling A, Byron R, Groudine M (2006) The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev 20:1447–1457
Rohlf FJ, Marcus IF (1993) A revolution in morphometrics. Trends Ecol Evol 8:129–132
Schroeder W, Matin K, Lorensen B (2003) The visualization toolkit, an object-oriented approach to 3D graphics, 3rd edn. Kitware, New York
Sexton T, Schober H, Fraser P, Gasser S (2007) Gene regulation through nuclear organization. Nat Struct Mol Biol 14:1049–1055
SkalnÃková M, Kozubek S, Lukášova E, Bártová E, Jirsová P, Cafourková A, Koutná I, Kozubek M (2000) Spatial arrangement of genes, centromeres and chromosomes in human blood cell nuclei and its changes during the cell cycle, differentiation and after irradiation. Chromo Res 8:487–499
Solovei I, Walter J, Cremer M, Habermann F, Schermelleh L, Cremer T (2002) FISH: a practical approach, Ch. 7 FISH on three-dimensionally preserved nuclei. Oxford University Press, Oxford, pp 119–157
Soutoglou E, Misteli T (2007) Mobility and immobility of chromatin in transcription and genome stability. Curr Opin Genet Dev 17:435–442
Sproul D, Gilbert N, Bickmore W (2005) The role of chromatin structure in regulating the expression of clustered genes. Nat Rev Genet 6:775–781
Walter J, Joffe B, Bolzer A, Albiez H, Benedetti P, Müller S, Speicher M, Cremer T, Cremer M, Solovei I (2006) Towards many colors in FISH on 3D-preserved interphase nuclei. Cytogenet Genome Res 114:367–378
Yang S, Götze S, Mateos-Langerak J, van Driel R, Eils R, Rohr K (2007) Variability analysis of the large-scale structure of interphase chromatin fiber based on statistical shape theory. In: Advances in mass-data, analysis of images and signals in medicine, biotechnology and chemistry (MDA). Springer-Verlag, Berlin, pp 37–46
Yang S, Köhler D, Teller K, Cremer T, Baccon PL, Heard E, Eils R, Rohr K (2008) Nonrigid registration of 3-d multichannel microscopy images of cell nuclei. IEEE Trans Image Process 17(4):493–499
Yokota H, van den Engh G, Jearst J, Sachs R, Trask B (1995) Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human g0/g1 interphase nucleus. J Cell Biol 130:1239–1249
Zlatanova J, Leuba S, van Holde K (1998) Chromatin fiber structure: morphology, molecular determinants, structural transitions. Biophys J 74:2554–2566
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Netherlands
About this chapter
Cite this chapter
Yang, S. et al. (2011). Statistical Shape Theory and Registration Methods for Analyzing the 3D Architecture of Chromatin in Interphase Cell Nuclei. In: Adams, N., Freemont, P. (eds) Advances in Nuclear Architecture. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9899-3_4
Download citation
DOI: https://doi.org/10.1007/978-90-481-9899-3_4
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-9898-6
Online ISBN: 978-90-481-9899-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)