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

Abstract

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.

Conformational properties of compact polymers

“…(5) we obtain c 2 = 1.140 (6) c 3 = 1.43(2) c 4 = 1.488 (24) The values are compatible with the ones calculated directly by a fit to the simulation data within the range of the errors. Deviations become large for larger moments reflecting the approximative character of the scaling function P (r).…”

Chromatin folding – from biology to polymer models and back

“…Local chromatin folding is related to the local transcriptional activity and gene density (Goetze et al, 2007a), and to replication timing (Ryba et al, 2010). Furthermore, the transcriptional state of a chromosome and its subchromosomal domains affect chromatin positioning inside the nucleus (Janicki et al, 2004).…”

“…One is that individual chromosomes occupy discrete domains in the interphase nucleus -named chromosome territories -which intermingle only to a limited extent (Cremer and Cremer, 2010). Similarly, different parts of a chromosome also only interact very little (Dietzel et al, 1998;Goetze et al, 2007a;Goetze et al, 2007b). Another organisational principle is based on the finding that mammalian interphase chromosomes are made up of a large number of structural domains, each of which are on averagẽ 1 Mb, that correspond to DNA replication units (Ryba et al, 2010).…”

p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells

“…However, for many genes transcriptional activity does not always correlate with radial distribution. Rather, the positioning of these genes is determined by the gene density of the corresponding genomic loci or by other factors, such as the proximity to distinct nuclear bodies, that facilitate or inhibit transcription (Brown et al, 2008;Goetze et al, 2007;Küpper et al, 2007;Mao et al, 2011;Yang et al, 2011).…”