Dai Yulin, Li Chao, Pei Guangsheng, Dong Xiao, Ding Guohui, Zhao Zhongming, Li Yixue, Jia Peilin
Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin St. Suite 820, Houston, TX, 77030, USA.
Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Rd, Shanghai, 200031, People's Republic of China.
BMC Syst Biol. 2018 Dec 21;12(Suppl 8):140. doi: 10.1186/s12918-018-0643-1.
Chromatin interactions medicated by genomic elements located throughout the genome play important roles in gene regulation and can be identified with the technologies such as high-throughput chromosome conformation capture (Hi-C), followed by next-generation sequencing. These techniques were wildly used to reveal the relative spatial disposition of chromatins in human, mouse and yeast. Unlike metazoan where CTCF plays major roles in mediating chromatin interactions, in yeast, the transcription factors (TFs) involved in this biological process are poorly known.
Here, we presented two computational approaches to estimate the TFs enriched in the chromatin physical inter-chromosomal interactions in yeast. Through the Chi-square method, we found TFs whose binding data are differentially distributed in different interaction groups, including Cin5, Stp1 and Sut1, whose binding data are negatively correlated with the chromosome spatial distance. A multivariate linear regression model was employed to estimate the potential contribution of different transcription factors against the physical distance of chromosomes. Rlr1, Set12 and Dig1 were found to be top positively participated in these chromosomal interactions. Ste12 was highlighted to be involved in gene reposition. Overall, we found 10 TFs enriched from both computational approaches, potentially to be involved in inter-chromosomal interactions.
No transcription factor (TF) in our study was found to have a dominant impact on the inter-chromosomal interaction as CTCF did in human or other metazoan, suggesting species without CTCF might have different regulatory systems in mediating inter-chromosomal interactions. In summary, we presented a systematic examination of TFs involved in chromatin interaction in yeast and the results provide candidate TFs for future studies.
由全基因组中的基因组元件介导的染色质相互作用在基因调控中发挥重要作用，可通过高通量染色体构象捕获（Hi-C）等技术，随后进行下一代测序来识别。这些技术被广泛用于揭示人类、小鼠和酵母中染色质的相对空间布局。与后生动物中CTCF在介导染色质相互作用中起主要作用不同，在酵母中，参与这一生物学过程的转录因子（TFs）鲜为人知。
在此，我们提出了两种计算方法来估计酵母染色质物理染色体间相互作用中富集的转录因子。通过卡方方法，我们发现其结合数据在不同相互作用组中差异分布的转录因子，包括Cin5、Stp1和Sut1，其结合数据与染色体空间距离呈负相关。采用多元线性回归模型来估计不同转录因子对染色体物理距离的潜在贡献。发现Rlr1、Set12和Dig1在这些染色体相互作用中积极参与程度最高。Ste12被强调参与基因重定位。总体而言，我们从两种计算方法中发现了10个富集的转录因子，可能参与染色体间相互作用。
在我们的研究中，未发现转录因子对染色体间相互作用有像人类或其他后生动物中CTCF那样的主导影响，这表明没有CTCF的物种在介导染色体间相互作用时可能有不同的调控系统。总之，我们对酵母中参与染色质相互作用的转录因子进行了系统研究，结果为未来研究提供了候选转录因子。
