The structure-function link of compensated chromatin in Drosophila

Abstract

All the aspects of transcription are controlled by complexes that modify or remodel chromatin at the level of individual genes, gene clusters, or whole chromosomes. The MSL complex that is responsible for dosage compensation in Drosophila is an example of complexes that operate at the whole-chromosome level on the transcription of individual genes. Recent experiments using traditional genetic analysis, molecular cytology, chromatin immunoprecipitation, or microarray technology have characterized the function of the two known enzymatic components of the MSL core complex and have identified the sequence characteristics that allow spreading of the complex along the X chromosome and a specific histone modification of active X-linked genes to which it is attracted. Further progress in understanding the function of this complex will benefit from biophysical approaches.

Figure 1. Spreading of the MSL complex along the X chromosome

The MSL complex assembles at the loci of the two roX genes that are located on the X chromosome. This is necessary because the roX RNAs are unstable unless they associate with some of the protein subunits of the complex. Assembled complexes then access the many sites along the X chromosome for which they have different levels of affinity. Ultimately the MSL complexes associate with those X-linked genes whose transcription is thereby enhanced.

Figure 2. Structure of a chromatin fiber

The interaction of neighboring nucleosomes via the N-termilal tails of their core histones can be modified by covalent modifications such as the acetylation of histone H4 at lysine 16 (Reprinted with permission [51]).

Figure 3. Example of a topological analysis of a plasmid subjected to dosage compensation

(a) Topoisomers are resolved in a chloroquine-containing gel. (b) Histogram representation of the topoisomers. Upper panel corresponds to the compensated plasmid; lower panel is a non-compensated control plasmid. The height of a bar represents the intensity of the corresponding bands in the gel. NC is the position of the nicked plasmid in the gel. The difference in the relative position of the two topoisomer distributions indicates a difference in the nucleosomal organization in the two plasmids.