Genetics: Gene Expression

In most organisms, genes are composed of discrete segments of DNA. Genes code for all of the proteins and structural RNA molecules used by cells within an organism. The coding segments of genes are often flanked by segments, or elements, that provide regulatory information. Regulatory elements control gene expression— the process that produces a functional protein or RNA molecule from the encoding DNA. Many steps in the control of gene expression are similar between prokaryotes (organisms, such as bacteria, that lack a nucleus) and eukaryotes (organisms that have a nucleus), and between simple and complex eukaryotes, although some features differ among these classes of organisms. Except where noted, the discussion below focuses on complex eukaryotes.

Regulatory DNA. Regulatory DNA includes several types of sequence elements that dictate when and how a gene is expressed. Among the most important of these are the promoters—the sequences that direct the start of transcription (the process that transcribes DNA into RNA; discussed below). Regulatory DNA elements also determine under what environmental, developmental, or physiological circumstances a gene is transcribed. Regulatory elements may stimulate or repress transcription by directly binding specific transcriptional activator or repressor proteins. They may also stimulate or repress transcription indirectly by binding proteins that alter the compaction of the DNA, and hence the accessibility of the promoters and other elements to binding proteins. Promoters and some regulatory elements are generally within a few hundred base pairs of the first coding segment of a gene. Other regulatory elements, particularly those that act indirectly, can be many thousands of base pairs away from genes.

Chromatin. DNA is virtually never naked (devoid of proteins) in cells. Rather, DNA in cells is packaged into chromatin—a complex of DNA and protein. Minimally, DNA is bound by histones, proteins that form a positively charged core around which 150 to 200 nucleotides of DNA are wrapped. Each core histone-DNA complex defines a nucleosome. Nucleosomes are separated by short DNA segments or linkers, which are bound by a noncore histone. Many other proteins bind nucleosomal DNA. Some of these regulate the higher order organization of nucleosomal DNA into secondary coils or folded threads, which in turn are organized into large loops, the bases of which are anchored to the nuclear matrix. Chromatin loops may define domains of heterochromatin, which is highly compact and relatively inaccessible to the transcription machinery, or euchromatin, which is relatively open and accessible to the transcription machinery.

Noncoding DNA. The coding segments of genes (exons) are often interspersed with relatively large noncoding segments (introns). Introns are initially transcribed into RNA but are subsequently removed by the process of RNA splicing. The functions of introns are not well understood, but at least some introns contain transcriptional control elements. In addition, some introns contain sequences that bind the nuclear matrix, and hence may influence whether genes are in heterochromatic or euchromatic chromatin loops.

Complex eukaryotic genomes contain other large DNA segments that do not encode genes. Some of these are important structural components of chromosomes (e.g., telomeres and centromeres). Others have no obvious structural or regulatory role, though understanding of noncoding DNA sequences is still very incomplete.