Chromocenter

 The salivary gland nuclei of Drosophila melanogaster contain polytene chromosomes. These specialized chromosomes essentially contain duplicated repeats of the DNA in the entire chromosome. Polytene chromosomes are fused at their centromeres to form the chromocenter . This specialized chromosomal domain in Drosophila consists of constitutive heterochromatin. The DNA sequences within the chromocenter consist of two types of repeats. One type that is assembled into a-heterochromatin is composed of highly repeated simple DNA sequences, whereas the second, b-type is more complex. Structural components of heterochromatin at the chromocenter have been identified (1). The best-characterized protein that accumulates selectively at the chromocenter is known as heterochromatin protein 1 (HP1). Antibodies to HP1 colocalize with the type of DNA repeat found in b-heterochromatin called the Dr.D element (2). This is at the edges of the chromocenter in what is termed pericentric heterochromatin.

HP1 contains a protein motif that is found in other chromatin binding proteins and is known as the chromodomain (for chromatin organization modifier). Recent studies have established that the chromodomain family of proteins comprises more than 40 members (3) that can be subdivided into two major groups. Proteins, such as HP1, contain both an amino-terminal chromodomain and a carboxy-terminal “shadow” chromodomain (4). The amino-terminal chromodomain directly binds to heterochromatin, whereas the carboxy-terminal “shadow” chromodomain determines nuclear localization and assists in binding to chromatin (5). The second group of proteins relies on interactions with other proteins to target association with particular chromatin domains (6). The structure of the chromodomain was recently determined using NMR (7). The chromodomain has strong homology to two archaebacterial DNA-binding proteins. However, the eukaryotic chromodomain does not interact with DNA and is involved in protein-protein interactions. Each chromodomain consists of an amino-terminal, three-stranded, antiparallel beta sheet that folds against a carboxy-terminal alpha-helix. The presence of both a chromodomain and a shadow chromodomain are thought to allow proteins, such as HP1, to function as adapters in assembling large multicomponent proteins.

The chromocenter is a useful chromosomal domain for identifying the structural components of heterochromatin and potentially for actually understanding how heterochromatin is organized at a molecular level. The formation of the chromocenter indicates how similar nucleoprotein complexes that share common structural components can self-associate. It provides a nice example of a specialized nuclear compartment that is assembled so that depends on protein–nucleic acid interactions.

References

1.T. C. James and S. C. R. Elgin (1986) Mol. Cell Biol. 6, 3862–3872. 

2. G. L. G. Miklos, M.-T. Yamamota, J. Davies, and V. Pirotta (1986) Proc. Natl. Acad. Sci. USA 85, 2051–2055. 

3. E. V. Koonin, S. B. Zhou, and J. C. Lucchesi (1995) Nucl. Acids Res. 23, 4229–4233. 

4. R. Aasland and A. F. Stewart (1995) Nucl. Acids Res. 23, 3168–3173. 

5. J. S. Platero, T. Hartnett, and J. C. Eissenberg (1995) EMBO J. 14, 3977–3986. 

6. A. Lorentz, K. Ostermann, O. Fleck, and H. Schmidt (1994) Gene 143, 1–8. 

7. L. J. Ball et al. (1997) EMBO J. 16, 2473–2481.