Molecular mechanisms of chromatin structure changes at position effect variegation

Heterochromatic position effect variegation (PEV) of the gene comprises euchromatic gene inhibition upon its transition in the area of heterochromatin either at the same chromosome, for example, in case of inversions (cis-acting PEV), or at the contact of the euchromatic gene with the heterochromatin associated with the allele of the same gene in the homologous chromosome in the three-dimentional nuclear volume (trans-acting PEV). The reverse PEV consists in heterochromatic gene inhibition in case it is placed in euchromatic environment. Most PEV data were obtained using genetic system of Drosophila melanogaster that has four chromosomes combine in the chromocenter. Heterochromatic cis-acting PEV often takes place in case of invertions such as In(2)A4; In(1)wm4. Molecular mechanisms of cis-acting PEV include expression level changes of several genes due to the changes in the quantities of specific histone modifications, heterochromatin proteins (HP1) and specific small RNA including piRNA. In case of cis-acting PEV the distribution of heterochromatic modifications (H3K9me2/3) and main heterochromatic protein (heterochromatin protein HP1a) from the heterochromatin to the euchromatin area is well studied that is associated with the expression inhibition of several genes. Heterochromatic trans-acting PEV has been thoroughly investigated only in a few cases including the invertion In(2)A4 and satellite DNA fragment insertion in brown gene (bwD). In both cases genomic rearrangements took place at the second chromosome of Drosophila melanogaster. Molecular mechanisms of trans-acting PEV are less studied than those of cis-acting PEV. It was shown that SU(VAR)2-HP2, SAYP, SETDB1 participate in trans-acting PEV in case of the inversion In(2)A4. Perspective studies in the field of cis- and trans-acting PEV include the role of prod and D1 mutations that influence the integrity of Drosophila melanogaster chromocenters.