Sequence and chromatin determinants of transcription factor binding and the establishment of cell type-specific binding patterns

Publication date: Available online 19 October 2019Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Divyanshi Srivastava, Shaun MahonyAbstractTranscription factors (TFs) selectively bind distinct sets of sites in different cell types. Such cell type-specific binding specificity is expected to result from interplay between the TF's intrinsic sequence preferences, cooperative interactions with other regulatory proteins, and cell type-specific chromatin landscapes. Cell type-specific TF binding events are highly correlated with patterns of chromatin accessibility and active histone modifications in the same cell type. However, since concurrent chromatin may itself be a consequence of TF binding, chromatin landscapes measured prior to TF activation provide more useful insights into how cell type-specific TF binding events became established in the first place. Here, we review the various sequence and chromatin determinants of cell type-specific TF binding specificity. We identify the current challenges and opportunities associated with computational approaches to characterizing, imputing, and predicting cell type-specific TF binding patterns. We further focus on studies that characterize TF binding in dynamic regulatory settings, and we discuss how these studies are leading to a more complex and nuanced understanding of dynamic protein-DNA binding activities. We propose that TF binding activities at individual sites can be viewed along a two-dimen...

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - October 19, 2019 Category: Genetics & Stem Cells Source Type: research