Journal
ANNUAL REVIEW OF GENETICS, VOL 46
Volume 46, Issue -, Pages 43-68Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-genet-110711-155437
Keywords
gene regulation; cis-regulatory module; cooperativity; DNA accessibility; chromosomal interactions
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Funding
- NIDDK NIH HHS [5T32DK07328, T32 DK007328] Funding Source: Medline
- NIGMS NIH HHS [R01 GM054510, GM54510, T32 GM007088] Funding Source: Medline
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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.
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