Institut de Génomique Fonctionnelle de Lyon, Univ Lyon, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, Univ Claude Bernard Lyon 1, Lyon, France.
Univ Lyon, ENS de Lyon, Univ Claude Bernard Lyon 1, CNRS Laboratoire de Physique, Lyon, France.
Biophys J. 2018 May 22;114(10):2308-2316. doi: 10.1016/j.bpj.2018.02.025. Epub 2018 Mar 24.
Nucleosome-depleted regions around which nucleosomes order following the "statistical" positioning scenario were recently shown to be encoded in the DNA sequence in human. This intrinsic nucleosomal ordering strongly correlates with oscillations in the local GC content as well as with the interspecies and intraspecies mutation profiles, revealing the existence of both positive and negative selection. In this letter, we show that these predicted nucleosome inhibitory energy barriers (NIEBs) with compacted neighboring nucleosomes are indeed ubiquitous to all vertebrates tested. These 1 kb-sized chromatin patterns are widely distributed along vertebrate chromosomes, overall covering more than a third of the genome. We have previously observed in human deviations from neutral evolution at these genome-wide distributed regions, which we interpreted as a possible indication of the selection of an open, accessible, and dynamic nucleosomal array to constitutively facilitate the epigenetic regulation of nuclear functions in a cell-type-specific manner. As a first, very appealing observation supporting this hypothesis, we report evidence of a strong association between NIEB borders and the poly(A) tails of Alu sequences in human. These results suggest that NIEBs provide adequate chromatin patterns favorable to the integration of Alu retrotransposons and, more generally to various transposable elements in the genomes of primates and other vertebrates.
最近有研究表明,在“统计”定位场景下,核小体周围的无核小体区域的顺序在人类的 DNA 序列中被编码。这种内在的核小体有序性与局部 GC 含量的波动以及种间和种内突变模式强烈相关,揭示了正选择和负选择的存在。在这封信中,我们表明,这些预测的核小体抑制能量障碍(NIEB)与压缩的相邻核小体确实在所有测试的脊椎动物中普遍存在。这些 1kb 大小的染色质模式广泛分布在脊椎动物染色体上,总体上覆盖了基因组的三分之一以上。我们之前在人类中观察到这些全基因组分布区域的偏离中性进化,我们将其解释为一种可能的选择,即开放、可及和动态的核小体阵列,以特定于细胞类型的方式持续促进核功能的表观遗传调控。作为支持这一假设的第一个非常有吸引力的观察结果,我们报告了证据表明,NIEB 边界与人类 Alu 序列的 poly(A)尾巴之间存在强烈关联。这些结果表明,NIEB 提供了有利于 Alu 反转录转座子整合的合适染色质模式,更普遍地说,为灵长类动物和其他脊椎动物基因组中的各种转座元件提供了合适的染色质模式。