Transcription factor-specific epigenomic codes.

<p>(A) An interaction network between TFs (orange nodes) and epigenetic modifications (blue nodes) in mES cells (p-value cutoff = 0.05). The interactions include positive (red edges) and negative correlations (green edges) of TF binding and epigenetic marks. This network suggests that each TF has its specific epigenetic marks for interaction. (B) TF-specific epigenomic motifs. The influences of every epigenetic mark to the binding of a TF ( in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003367#pcbi.1003367.e041" target="_blank">Equation (5)</a>) are summarized as a column vector. In analogy to matrix presentation of DNA recognition motifs, we propose to use a column vector to represent the epigenomic motif of a TF. Each column represents an epigenomic motif {, …, }, and the first column is {, …, }.</p

Epigenomic regulation of transcriptional noise.

<p>Transcriptional noise is introduced when the binding probability (y axis) between a TF and its target TFBS falls into a particular range (horizontal yellow band). There is nearly no noise above or below this range, because almost all cells would uniformly have this target TFBS in the bound or the unbound state, respectively. The binding probabilities are constrained by the realistic range (vertical blue band) of TF concentrations in eukaryotic cells (x axis). (A) In the presence of a strong binding site (S), the binding probabilities are shown as functions of the TF concentration and the presence of epigenomic marks (Red curve: activation mark, green: no epigenomic marks, blue: repression mark). Activation marks suppress transcriptional noise by reducing the range of feasible binding probabilities, whereas repression marks enhance transcriptional noise. (B) In the presence of a weak binding site (W), both activation (red) and repression (blue) marks tend to suppress transcriptional noise.</p

Chemical Modification-Assisted Bisulfite Sequencing (CAB-Seq) for 5‑Carboxylcytosine Detection in DNA

5-Methylcytosine (5mC) in DNA can be oxidized stepwise to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the TET family proteins. Thymine DNA glycosylase can further remove 5fC and 5caC, connecting 5mC oxidation with active DNA demethylation. Here, we present a chemical modification-assisted bisulfite sequencing (CAB-Seq) that can detect 5caC with single-base resolution in DNA. We optimized 1-ethyl-3-[3-dimethylaminopropyl]­carbodiimide hydrochloride (EDC)-catalyzed amide bond formation between the carboxyl group of 5caC and a primary amine group. We found that the modified 5caC can survive the bisulfite treatment without deamination. Therefore, this chemical labeling coupled with bisulfite treatment provides a base-resolution detection and sequencing method for 5caC