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Molecular and Cellular Biology, June 2007, p. 4475-4487, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.00208-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Three-Dimensional Structure of Human Interphase Chromosomes Is Related to the Transcriptome Map{triangledown}

Sandra Goetze,1,{dagger} Julio Mateos-Langerak,1,{dagger} Hinco J. Gierman,2 Wim de Leeuw,3 Osdilly Giromus,1 Mireille H. G. Indemans,2 Jan Koster,2 Vladan Ondrej,4 Rogier Versteeg,2 and Roel van Driel1*

Swammerdam Institute for Life Sciences, University of Amsterdam, BioCentrum Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands,1 Department of Human Genetics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands,2 National Research Institute for Mathematics and Computer Science, Kruislaan 413, 1098 SJ Amsterdam, The Netherlands,3 Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic4

Received 4 February 2007/ Returned for modification 1 March 2007/ Accepted 29 March 2007

The three-dimensional (3D) organization of the chromosomal fiber in the human interphase nucleus is an important but poorly understood aspect of gene regulation. Here we quantitatively analyze and compare the 3D structures of two types of genomic domains as defined by the human transcriptome map. While ridges are gene dense and show high expression levels, antiridges, on the other hand, are gene poor and carry genes that are expressed at low levels. We show that ridges are in general less condensed, more irregularly shaped, and located more closely to the nuclear center than antiridges. Six human cell lines that display different gene expression patterns and karyotypes share these structural parameters of chromatin. This shows that the chromatin structures of these two types of genomic domains are largely independent of tissue-specific variations in gene expression and differentiation state. Moreover, we show that there is remarkably little intermingling of chromatin from different parts of the same chromosome in a chromosome territory, neither from adjacent nor from distant parts. This suggests that the chromosomal fiber has a compact structure that sterically suppresses intermingling. Together, our results reveal novel general aspects of 3D chromosome architecture that are related to genome structure and function.

* Corresponding author. Mailing address: Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands. Phone: 31-20-525-5150. Fax: 31-20-525-7935. E-mail: van.driel{at}science.uva.nl

{triangledown} Published ahead of print on 9 April 2007.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, June 2007, p. 4475-4487, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.00208-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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