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Transcription factors (TFs) are proteins specifically involved in gene expression regulation. It is generally accepted in epigenetics that methylated nucleotides could prevent the TFs from binding to DNA fragments. However, recent studies have confirmed that some TFs have capability to interact with methylated DNA fragments to further regulate gene expression. Although biochemical experiments could recognize TFs binding to methylated DNA sequences, these wet experimental methods are time-consuming and expensive. Machine learning methods provide a good choice for quickly identifying these TFs without experimental materials. Thus, this study aims to design a robust predictor to detect methylated DNA-bound TFs. We firstly proposed using tripeptide word vector feature to formulate protein samples. Subsequently, based on recurrent neural network with long short-term memory, a two-step computational model was designed. The first step predictor was utilized to discriminate transcription factors from non-transcription factors. Once proteins were predicted as TFs, the second step predictor was employed to judge whether the TFs can bind to methylated DNA. Through the independent dataset test, the accuracies of the first step and the second step are 86.63% and 73.59%, respectively. In addition, the statistical analysis of the distribution of tripeptides in training samples showed that the position and number of some tripeptides in the sequence could affect the binding of TFs to methylated DNA. Finally, on the basis of our model, a free web server was established based on the proposed model, which can be available at https://bioinfor.nefu.edu.cn/TFPM/. [ABSTRACT FROM AUTHOR]

The methyl-specific restriction system of Streptomyces coelicolor A3(2) was analyzed by carrying out transformations with unmethylated and methylated pSET152 DNA. Streptomyces coelicolor was found to strongly restrict DNA methylated in vivo by the Dam, Dcm and Hsd modification systems of Escherichia coli. Hsd-modified DNA was restricted as strongly as Dam-modified DNA, even though there are significantly fewer sites on the plasmid; Dcm-modified plasmid was restricted more strongly then either Dam- or Hsd-modified DNA. Restriction of plasmid DNA modified in vitro by different methylases also showed a greater dependence on the methylated sequence than on the number of methylated sites. Streptomyces coelicolor mutants were constructed that lacked genes identified as the likely candidates for encoding methyl-specific restriction nucleases (the products of the SCO4213, SCO4631 and SCO2863 genes, as well as the SCO3261–SCO3262 operon) that are located in the laterally acquired genomic islands of the S. coelicolor chromosome; these mutants showed partial alleviation of methylated DNA restriction. Cloning of these genes in the close relative Streptomyces lividans increased the restriction of methylated DNA by this species, confirming their role as part of the methyl-specific restriction system of S. coelicolor. [ABSTRACT FROM AUTHOR]