Fig. 1.1 The organization of nuclear DNA. At the light microscopic level, the nuclear genetic material is organized into dispersed, transcriptionally active euchromatin or densely packed, transcriptionally inactive heterochromatin; chromatin can also be mechanically connected with the nuclear membrane, and nuclear membrane perturbation can thus influence transcription. Chromosomes (as shown) can only be visualized by light microscopy during cell division. During mitosis, they are organized into paired chromatids connected at centromeres; the centromeres act as the locus for the formation of a kinetochore protein complex that regulates chromosome segregation at metaphase. The telomeres are repetitive nucleotide sequences that cap the termini of chromatids and permit repeated chromosomal replication without loss of DNA at the chromosome ends. The chromatids are organized into short “P” (“petite”) and long “Q” (“next letter in the alphabet”) arms. The characteristic banding pattern of chromatids has been attributed to relative GC content (less GC content in bands relative to interbands), with genes tending to localize to interband regions. Individual chromatin fibers are composed of a string of nucleosomes—DNA wound around octameric histone cores—with the nucleosomes connected via DNA linkers. Promoters are noncoding regions of DNA that initiate gene transcription; they are on the same strand and upstream of their associated gene. Enhancers are regulatory elements that can modulate gene expression across distances of 100 kB or more by looping back onto promoters and recruiting additional factors that are needed to drive the expression of pre-mRNA species. The intronic sequences are subsequently spliced out of the pre-mRNA to produce the definitive message that includes exons that are translated into protein and 3′- and 5′-untranslated regions (UTR) that may have regulatory functions. In addition to the enhancer, promoter, and UTR sequences, noncoding elements are found throughout the genome; these include short repeats, regulatory factor binding regions, noncoding regulatory RNAs, and transposons.
and machinery required for assembling cells, tissues, and organisms, it is the noncoding regions of the genome that provide the critical “architectural planning.”
The major classes of functional non–protein-coding DNA sequences found in the human genome include (
Fig. 1.1