Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Bioinformatics. 2013 Jul 15;29(14):1713-7. doi: 10.1093/bioinformatics/btt288. Epub 2013 Jun 5.
In addition to alternative splicing, alternative polyadenylation has also been identified as a critical and prevalent regulatory mechanism in human gene expression. However, the mechanism of alternative polyadenylation selection and the involved factors is still largely unknown.
We use the ENCODE data to scan DNA functional elements, including chromatin accessibility and histone modification, around transcript cleavage sites. Our results demonstrate that polyadenylation sites tend to be less sensitive to DNase I. However, these polyadenylation sites have preference in nucleosome-depleted regions, indicating the involvement of chromatin higher-order structure rather than nucleosomes in the resultant lower chromatin accessibility. More interestingly, for genes using two polyadenylation sites, the distal sites show even lower chromatin accessibility compared with the proximal sites or the unique sites of genes using only one polyadenylation site. We also observe that the histone modification mark, histone H3 lysine 36 tri-methylation (H3K36Me3), exhibits different patterns around the cleavage sites of genes using multiple polyadenylation sites from those of genes using a single polyadenylation site. Surprisingly, the H3K36Me3 levels are comparable among the alternative polyadenylation sites themselves. In summary, polyadenylation and alternative polyadenylation are closely related to functional elements on the DNA level.
除了可变剪接，可变多聚腺苷酸化也被确定为人类基因表达中的一个关键且普遍的调控机制。然而，可变多聚腺苷酸化选择的机制和涉及的因素在很大程度上仍然未知。
我们使用 ENCODE 数据扫描 DNA 功能元件，包括染色质可及性和组蛋白修饰，在转录切割位点周围。我们的结果表明，多聚腺苷酸化位点往往对 DNase I 不敏感。然而，这些多聚腺苷酸化位点在核小体缺失区域有偏好，表明染色质高级结构的参与，而不是核小体，导致较低的染色质可及性。更有趣的是，对于使用两个多聚腺苷酸化位点的基因，与使用单个多聚腺苷酸化位点的基因的近端或唯一位点相比，远端位点显示出甚至更低的染色质可及性。我们还观察到，在使用多个多聚腺苷酸化位点的基因的切割位点周围，组蛋白修饰标记，组蛋白 H3 赖氨酸 36 三甲基化（H3K36Me3），表现出与使用单个多聚腺苷酸化位点的基因不同的模式。令人惊讶的是，在替代多聚腺苷酸化位点本身之间，H3K36Me3 水平相当。总之，多聚腺苷酸化和可变多聚腺苷酸化与 DNA 水平上的功能元件密切相关。
