PDF(Pubmed)
Abstract：
The linear DNA sequence of mammalian chromosomes is organized in large blocks of DNA with similar sequence properties, producing a pattern of dark and light staining bands on mitotic chromosomes. Cytogenetic banding is essentially invariant between people and cell-types and thus may be assumed unrelated to genome regulation. We investigate whether large blocks of Alu-rich R-bands and L1-rich G-bands provide a framework upon which functional genome architecture is built. We examine two models of large-scale chromatin condensation: X-chromosome inactivation and formation of senescence-associated heterochromatin foci (SAHFs). XIST RNA triggers gene silencing but also formation of the condensed Barr Body (BB), thought to reflect cumulative gene silencing. However, we find Alu-rich regions are depleted from the L1-rich BB, supporting it is a dense core but not the entire chromosome. Alu-rich bands are also gene-rich, affirming our earlier findings that genes localize at the outer periphery of the BB. SAHFs similarly form within each territory by coalescence of syntenic L1 regions depleted for highly Alu-rich DNA. Analysis of senescent cell Hi-C data also shows large contiguous blocks of G-band and R-band DNA remodel as a segmental unit. Entire dark-bands gain distal intrachromosomal interactions as L1-rich regions form the SAHF. Most striking is that sharp Alu peaks within R-bands resist these changes in condensation. We further show that Chr19, which is exceptionally Alu rich, fails to form a SAHF. Collective results show regulation of genome architecture corresponding to large blocks of DNA and demonstrate resistance of segments with high Alu to chromosome condensation.
摘要：
哺乳动物染色体的线性DNA序列被组织在具有相似序列特性的大块DNA中，在有丝分裂染色体上产生深色和浅色染色带的模式。细胞遗传学条带在人和细胞类型之间基本上是不变的，因此可以认为与基因组调节无关。我们研究了富含Alu的R带和富含L1的G带的大块是否提供了构建功能性基因组结构的框架。我们研究了两种大规模染色质凝聚模型：X染色体失活和衰老相关的异染色质灶（SAHFs）的形成。XISTRNA触发基因沉默，但也形成浓缩的Barr体（BB），被认为反映了累积的基因沉默。然而,我们发现富含Alu的区域从富含L1的BB中耗尽，支持它的是一个致密的核心，但不是整个染色体。富含Alu的条带也富含基因，肯定了我们早期的发现，即基因位于BB的外围。SAHFs通过减少高度富含Alu的DNA的合成L1区域的合并在每个区域内类似地形成。对衰老细胞Hi-C数据的分析还显示了G带和R带DNA重构为片段单位的大的连续块。当富含L1的区域形成SAHF时，整个暗带获得远端染色体内相互作用。最引人注目的是R带内的尖锐Alu峰抵抗这些冷凝的变化。我们进一步表明，Chr19特别富有，无法形成SAHF。集体结果显示了对应于大块DNA的基因组结构的调节，并证明了具有高Alu的片段对染色体凝聚的抗性。
