PROSITE documentation PDOC52051

CXC MSL2-type domain profile

Organisms with different numbers of sex chromosomes between males and females face the problem of an unequal dosage of genes from sex chromosomes. In humans and fruit flies, two X chromosomes define the female sex, whereas males have only one X in addition to the Y chromosome. This unbalanced situation diminishes the vitality of the organism and therefore generated an evolutionary pressure to compensate for the reduced dosage of X chromosomal genes. In mammals and fruit flies, this is achieved by selective transcriptional activation of X chromosomal genes through histone acetylation. Whereas in Drosophila melanogaster, the X chromosome is only boosted in males, in mammals, all X chromosomes in both sexes are activated followed by the selective inactivation of one X in females.

In drosophilid species, the process of dosage compensation involves a general modification of the chromatin structure of the X chromosome in males. This dosage compensation process is mediated, for most X chromosome genes, by the dosage compensation complex (DCC) or male-specific lethal (MSL) complex, which contains at least five proteins MSL1, MSL2, MSL3, males absent on the first (MOF) and maleless (MLE) and two non-coding RNAs roX1 and roX2. A module consisting of only MSL2 and MSL1 recognizes a small number of primary targeting elements on the X that are called the 'chromosomal entry sites' (CES), or 'high-affinity sites' (HAS).

MSL2 is characterized by several domains: a RING finger mediates the interaction with MSL1, a conserved cysteine-rich domain similar to the CXC domain of Enhancer of Zeste (E[Z]) proteins (see <PDOC51633>) and a basic, proline-rich patch (Pro/Bas patch). The MSL2-type CXC dpmain has a DNA binding function as it can mediate the DNA binding of the MSL2-MSL1 heteromer [1,2,3,4].

The MSL2-type CXC domain is remarkable by having 9 invariant Cys within about 50 residue region. The pattern of conserved residues characteristic of the MSL2-type CXC domain can be generalized as C-X-C-X(10-11)-C-X(4)-C-X-C-X(6)-C-X(2)-C-X-C-X(2)-C. Each MSL2-type CXC domain is composed of several loops and a short α helix that encircle three Zn ions by two rounds in a right-handed manner. The three Zn ions are coordinated by six terminal and three bridging cysteines (see <PDB:4RKH>) [3,4].

Mammals contain a similar MSL complex that is composed of orthologs of MSL1, MSL2, MSL3, and MOF and conducts H4K16 acetylation of all chromosomes [4].

The profile we developed covers the entire MSL2-type CXC domain.