Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.
Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.
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DOI：
10.1101/gr.141028.112
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发表时间：
2013-02
期刊：
影响因子：
7
通讯作者：
van Steensel B
中科院分区：
文献类型：
--
作者：
Meuleman W;Peric-Hupkes D;Kind J;Beaudry JB;Pagie L;Kellis M;Reinders M;Wessels L;van Steensel B
在后生动物中，核纤层被认为在间期染色体的空间组织中发挥重要作用，通过为称为核纤层相关结构域（LAD）的大基因组片段提供锚定位点。这些LAD中的一些是细胞类型特异性的，而许多其他LAD则与纤层组成性相关。组成型LAD（cLAD）可能有助于基础染色体结构。通过比较小鼠和人的纤层相互作用图谱，我们发现cLAD的大小和基因组位置是高度保守的。此外，cLADs耗尽同线性断点，指向进化选择压力以保持cLADs完整。巧合的是，cLAD的整体序列保守性较低。相反，cLAD普遍以高A/T含量的长DNA片段为特征。细胞类型特异性LAD在胚胎干细胞中也倾向于遵循这种“A/T规则”，但在分化细胞中则不然。这表明A/T规则代表了一种默认的定位机制，在血统承诺期间被局部否决。旁系同源物的分析表明，在进化过程中，A/T含量的变化驱动了基因的搬迁和从核纤层，与表达水平的变化密切相关。总之，这些结果表明，哺乳动物基因组的空间组织是高度保守的，并与当地的核苷酸组成紧密相连。
In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this “A/T rule” in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.
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DOI：
10.1083/jcb.200804155
发表时间：
2009-01-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Malhas AN;Lee CF;Vaux DJ
通讯作者：
Vaux DJ
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
7
作者：
Pollard, Katherine S.;Hubisz, Melissa J.;Siepel, Adam
通讯作者：
Siepel, Adam
影响因子：
2.5
作者：
Bartova, Eva;Galiova, Gabriela;Kozubek, Stanislav
通讯作者：
Kozubek, Stanislav
影响因子：
64.8
作者：
Nora, Elphege P.;Lajoie, Bryan R.;Schulz, Edda G.;Giorgetti, Luca;Okamoto, Ikuhiro;Servant, Nicolas;Piolot, Tristan;van Berkum, Nynke L.;Meisig, Johannes;Sedat, John;Gribnau, Joost;Barillot, Emmanuel;Bluethgen, Nils;Dekker, Job;Heard, Edith
通讯作者：
Heard, Edith