Anthropology and Human Genetics

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Our concept of a functional organization of nuclear architecture

Chromosomes occupy distinct territories (CTs) in the interphase nucleus. Increasing experimental evidence has supported a functional organization of CTs being composed of a chromatin compartment (CC) harboring interconnected ∼1 Mb chromatin domains (CDs) and an interchromatin compartment (IC) channel system. CD clusters of active CTs are lined by a layer of low density chromatin, the perichromatin region (PR) with a variable size of up to 150 nm (Fakan S & van Driel R. 2007, Semin Cell Dev Biol 18:676-81).

This PR network is co-aligned with the IC network which pervades CDs throughout the nucleus and ultimately leads to nuclear pores thus providing a highly organized, spatially contiguous compartment that likely serves as a system for the guided diffusion of macromolecules. PR and IC form together an intricate nuclear compartment which is considered as the fundamental nuclear sub-compartment where transcription, DNA-replication and repair occurs. An organization of chromatin being comprised of domains with a size range between 200 kb up to ∼1 Mb was recently confirmed by chromosome conformation capturing (e.g. Hi-C) based approaches where such chromatin domains are defined as topology associated domains (TADs) (Dixon JR, et al. 2012, Nature 485:376-380; Gibcus JH & Dekker J. 2013 Mol Cell 49:773-782).

It is suggested that such a fractal organization minimizes detrimental chromatin fibres/loop entanglements (Mirny LA; 2011, Chromosome Res 19:37-51), facilitates the local ‘opening’ and ‘closure’ of ~1 Mbp CDs, small-scale chromatin movements in cell nuclei on functional demands, as well as the structural transformation of chromosome territories (CTs) into mitotic chromosomes. A domain organization of the genome likely provided an important selective advantage already at the roots of eukaryote evolution.


Relevant publications from our group:

Cremer T and Cremer C (2001) Chromosome Territories, Nuclear Architecture and Gene Regulation in Mammalian Cells. Nature Rev Genet 2: 292-301

Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu S, Fauth C, Müller S, Eils R, Cremer C, Speicher MR, Cremer T (2005) Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes. PLoS Biol 3 (5): e157

Albiez H, Cremer M, Tiberi C, Vecchio L, Schermelleh L, Dittrich S, Küpper K, Joffe B, Thormeyer T, von Hase J, Yang S, Rohr K, Leonhardt H, Solovei I, Cremer C, Fakan S, Cremer T (2006) Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks. Chromosome Res 14: 707-733

Cremer T, Cremer M, Dietzel S, Müller S, Solovei 1, Fakan S (2006) Chromosome territories – a functional nuclear landscape. Curr Opin Cell Biol 18: 307–316

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. Nature Rev Genet 8: 105-115

Rouquette J, Genoud C, Vazquez-Nin GH, Kraus B, Cremer T, Fakan S (2009) Revealing the high-resolution three-dimensional network of chromatin and interchromatin space: A novel electron-microscopic approach to reconstructing nuclear architecture. Chromosome Res. 17: 801-810

Markaki Y, Gunkel M, Schermelleh L, Beichmanis S, Neumann J, Heidemann M., Leonhardt H, Eick D, Cremer C, Cremer T (2010) Functional nuclear organization of transcription and DNA replication: a topographical marriage between chromatin domains and the interchromatin compartment. Cold Spring Harb Sym Quant. Biol., Nuclear Organization and Function 75: 475-492

Rouquette J, Cremer C, Cremer T, Fakan S (2010) Functional nuclear architecture studied by microscopy: Present and future. Int Rev Cell Mol Bio 282: 1-156

Strickfaden H, Zunhammer A, van Koningsbruggen S, Koehler D, Cremer T (2010) 4D chromatin dynamics in cycling cells: Theodor Boveri’s hypotheses revisited. Nucleus 1: 284-297

Cremer T and Cremer M (2010) Chromosome territories. Cold Spring Harb. Perspectives in Biology, 2, a003889

Cremer T, Markaki Y, Hübner B, Zunhammer A, Strickfaden H, Beichmanis S, Heß M, Schermelleh L, Cremer M and Cremer C (2012) Chromosome territory organisation within the nucleus (2012) Advances in Molecular Biology and Medicine (Vol. 1). Epigenetic Regulation and Epigenomics Edited by Robert A. Meyers.Wiley-VCH. Vol 1: 451-483