Roles of Lineage-Determining Transcription Factors in Establishing Open Chromatin: Lessons From High-Throughput Studies

Abstract

The interpretation of the regulatory information of the genome by sequence-specific transcription factors lies at the heart of the specification of cellular identity and function. While most cells in a complex metazoan organism express hundreds of such transcription factors, the underlying mechanisms by which they ultimately achieve their functional locations within different cell types remain poorly understood. Here, we contrast various models of how cell type-specific binding patterns may arise using available evidence from ChIP-Seq experiments obtained in tractable developmental model systems, particularly the hematopoietic system. The data suggests a model whereby relatively small sets of lineage-determining transcription factors jointly compete with nucleosomes to establish their cell type-specific binding patterns. These binding sites gain histone marks indicative of active cis-regulatory elements and define a large fraction of the enhancer-like regions differentiated cell types. The formation of these regions of open chromatin enables the recruitment of secondary transcription factors that contribute additional transcription regulatory functionality required for the cell type-appropriate expression of genes with both general and specialized cellular functions.