At one time it was anticipated that control of gene expression could be completely understood from nucleotide sequences within and flanking genes. This expectation has not been realized. The extensive database of gene sequences, promoter elements and regulatory factors developed over the past several years provides insight into parameters of transcriptional control and transcript processing. However, it is becoming increasingly evident that the linear representation of gene regulatory information is necessary but insufficient to support the plasticity of gene regulatory mechanisms that must be operative in vivo . Functional interrelationships between nuclear structure and gene expression are emerging.
Nucleosomal architecture regulates competency for crosstalk between promoter domains.
Nuclear reorganization is the striking and clinically relevant hallmark of many cancer cells. In addition to providing diagnostic markers for transformation and tumor progression, these alterations in components of nuclear structure reflect abrogation of regulatory mechanisms which mediate cell growth and phenotypic control. Recently there have been significant reports of nuclear reorganization in several neurological disorders, extending the paradigm of a requirement for structural integrity of the nucleus to support fidelity of gene expression. Historically, control of gene expression was conceptually and experimentally pursued as independent and minimally integrated questions. This independent pursuit of nuclear structure, compartmentalization and function has occurred in parallel with the appreciation that several components of nuclear architecture are associated with parameters of gene expression or control of specific classes of genes.