TI - Gene Positioning Relative to Subnuclear Domains . AB - Earlier studies describing correlations between gene silencing and perinuclear positioning were based on the comparisons of different cell types or developmental stages [19] , [20] , [50] , [51] . Such studies can theoretically be confounded by cell -specific differences in global spatial chromosomal arrangements [39] . It is thus important that peripheral positioning is now elicited in a model where transcriptional inactivity is ascribed to the selective absence of a direct transactivator . Previous studies have also shown that genes are preferentially transcribed in nuclear subdomains enriched in RNA polymerase II [17] , [52] , [53] . This has led to models postulating that active loci loop into domains with high local RNA polymerase II concentrations [17] , [54] . Our findings confirm that gene activity is associated with localization to PHOSphoserine-5 RNA polymerase II domains in primary cells , and furthermore demonstrate that association with such domains is linked to the function of a transcriptional activator . Importantly , the new results extend our understanding of this phenomenon by showing that relocation does not only occur with respect to domains enriched in RNA polymerase II , but also involves repositioning amongst compartments that differ in the composition of histone modifications known to be critically involved in transcriptional regulation , and that such domains display distinct radial distributions . Our integrated analysis of a transactivator -deficient model thus suggests that transcription-related gene positioning with respect to RNA polymerase II foci , distinct radial nuclear zones , and domains enriched in specific histone modifications might reflect different experimental measurements of a single biological phenomenon .