title: Disentangling the many layers of eukaryotic transcriptional regulation.
abstract: Regulation of gene expression in eukaryotes is an extremely complex process. In this review, we break down several critical steps, emphasizing new data and techniques that have expanded current gene regulatory models. We begin at the level of DNA sequence where cis-regulatory modules (CRMs) provide important regulatory information in the form of transcription factor (TF) binding sites. In this respect, CRMs function as instructional platforms for the assembly of gene regulatory complexes. We discuss multiple mechanisms controlling complex assembly, including cooperative DNA binding, combinatorial codes, and CRM architecture. The second section of this review places CRM assembly in the context of nucleosomes and condensed chromatin. We discuss how DNA accessibility and histone modifications contribute to TF function. Lastly, new advances in chromosomal mapping techniques have provided increased understanding of intra- and interchromosomal interactions. We discuss how these topological maps influence gene regulatory models.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Lelli
authors.forename: Matthew
authors.initials: M
authors.lastname: Slattery
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mann
mesh_terms: D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006657:Histones / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D050436:Regulatory Elements, Transcriptional; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors