Chapter 6 - Chromosomal Position Effects and Gene Variegation Impact in Pathologies英文教材.pdf
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chapter 6
chromosomal position
effects and Gene
Variegation: Impact in
pathologies
caroline Schluth-Bolard1,*, alexandre Ottaviani1,*, eric Gilson1,2,3,
and Frédérique Magdinier1,4
1Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon,
69364 Lyon Cedex 07
2Department of Medical Genetics, Archet 2 Hopital, CHU de Nice
3Laboratory of Biology and Pathology of Genomes, University of Nice-Sophia Antipolis,
CNRS UMR 6267/INSERM U998, Faculty of Medecine, Nice, France
4Laboratoire de Génétique Médicale et Génomique Fonctionnelle, Faculté de Médecine de
la Timone, 13385 Marseille Cedex 5, France 77
IntrOductIOn
The genome of higher eukaryotes is composed of thousands of genes and even more
interspersed non-coding sequences. Constraining up to tens of billions of bases within a
nucleus of a few microns in diameter requires a high level of DNA compaction that must
also exhibit high plasticity in order to allow efficient realization of cellular functions such
as replication, transcription, or repair. DNA sequence is the first determinant of chromatin
organization and cross-talks between the DNA sequence, the protein complexes involved in
the chromatin architecture and the structural components of the nucleus provide a proper
subnuclear environment that ensures correct spatial and temporal gene expression.
Each chromatin state can be defined by its level of compaction, its topological state,
the positioning and the spacing of nucleosomes, its histone code predicting how the
posttranslational modifications of specific amino acids of the core histones (H2A, H2B,
H3, and H4) are translated into distinct information [1], the presence of histone variants,
the covalent modification of the underlying DNA, its composition in
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