Each chromosome consists of one long molecule of DNA compacted by histone and nonhistone proteins. The five types of histones--H1, H2A, H2B, H3, and H4--are essential to the establishment of generalized chromosome structure. There are more than 1000 kinds of nonhistone proteins: Some are structural; others are active in replication and segregation; but most help determine the time and place of gene expression.
DNA-protein interactions create reversible levels of compaction.
The naked DNA wraps around core histones to form nucleosomes, which are secured by H1.
Models of higher-level compaction suggest that some sort of supercoiling condenses the nucleosomal fiber to a wider fiber. Nonhistone proteins then anchor this fiber to form loops and higher levels of compaction (perhaps in the form of rosettes and bunches of rosettes). In metaphase chromosomes, higher levels of folding compact DNA 10,000-fold.
In fully compacted metaphase chromosomes, the centromere and telomeres become visible under the microscope. Giemsa staining of metaphase chromosomes reveals highly reproducible banding patterns that researchers can use to locate genes, analyze chromosomal differences between species, and diagnose some genetic diseases.
Specialized elements are required for normal chromosome function.
Origins of replication are sites accessible for the binding of proteins that initiate replication. In eukaryotic chromosomes, many origins of replication ensure timely DNA replication.
Telomeres, composed of repetitive base sequences, protect the ends of chromosomes, ensuring their integrity. The enzyme telomerase helps reconstruct the complete telomere with each cell division.
Centromeres, which appear as constrictions in metaphase chromosomes, ensure proper segregation by holding sister chromatids together and by elaborating kinetochores, which properly attach sister chromatids to spindle fibers for mitosis and meiosis.
Chromosomal packaging influences gene activity.
Conditions that decondense selected areas of chromatin precede and facilitate gene expression. Puffs in Drosophila polytene chromosomes and the nucleoli in most interphase cells contain decondensed chromatin that is highly transcribed. Boundary elements called insulators delimit these areas of decompaction. Nucleosomes in the decompacted areas unwind to allow the initiation of transcription.
Extreme condensation silences gene expression. Extremely condensed chromosomal areas appear as darkly staining heterochromatin under the microscope. Position-effect variegation in Drosophila and Barr bodies in mammals are examples of the correlation between heterochromatin formation and a loss of gene activity.
