Hervé B, Coussement A, Gilbert T, Dumont F, Jacques S, Cuisset L, Chicard M, Hizem S, Bourdoncle P, Letourneur F, Dupont C, Vialard F, Choiset A, Dupont J-M
UFR des Sciences de la Santé Simone Veil, GIG, EA7404, Montigny le Bretonneux, France.
Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut Cochin, Université Paris Descartes, Paris, France.
Clin Genet. 2016 Jul;90(1):35-48. doi: 10.1111/cge.12731. Epub 2016 Mar 23.
The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression.
间期细胞核内染色质作为染色体领地（CTs）的组织和动态变化以及与转录调控的关系尚未完全明了。我们研究了染色体无序的一个自然实例：由13、18和21三体导致的非整倍体。我们推测一条染色体额外拷贝的存在会改变CT分布，进而扰乱转录活性。我们使用三维荧光原位杂交（3D-FISH）来研究来自核型正常或非整倍体妊娠的培养羊膜细胞和绒毛膜绒毛细胞中感兴趣染色体（18号和21号）的位置。我们研究了两种情况下细胞核和CTs的体积，并进行了转录组比较分析。在径向和相对CT位置方面，我们未观察到整倍体细胞和非整倍体细胞之间存在任何差异，这表明三体情况下相同的规则支配着核组织。我们观察到18号和21号CTs的体积较小。整体基因组表达谱突出了三体染色体上一部分基因表达的变化，而大多数转录变化涉及位于整倍体染色体上的基因。我们的结果表明，三体染色体上基因的剂量失衡与整体基因组表达紊乱有关。
