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

Divyanshi Srivastava, Shaun Mahony

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


Transcription 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-dimensional continuum of local sequence and chromatin context. Under this view, cell type-specific TF binding activities may result from either strongly favorable sequence features or strongly favorable chromatin context.

Original languageEnglish (US)
Article number194443
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Issue number6
StatePublished - Jun 2020

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics


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