RNA polymerases can be shared by a particular group of genes in a transcription "factory" in nuclei, where transcription may be coordinated in concert with the distribution of coexpressed genes in higher-eukaryote genomes. Moreover, gene expression can be modulated by regulatory elements working over a long distance. Here, we compared the conformation of a 130-kb chromatin region containing the mouse ␣-globin cluster and their flanking housekeeping genes in 14.5-day-postcoitum fetal liver and brain cells. The analysis of chromatin conformation showed that the active ␣1 and ␣2 globin genes and upstream regulatory elements are in close spatial proximity, indicating that looping may function in the transcriptional regulation of the mouse ␣-globin cluster. In fetal liver cells, the active ␣1 and ␣2 genes, but not the inactive gene, colocalize with neighboring housekeeping genes C16orf33, C16orf8, MPG, and C16orf35. This is in sharp contrast with the mouse ␣-globin genes in nonexpressing cells, which are separated from the congregated housekeeping genes. A comparison of RNA polymerase II (Pol II) occupancies showed that active ␣1 and ␣2 gene promoters have a much higher RNA Pol II enrichment in liver than in brain. The RNA Pol II occupancy at the gene promoter, which is specifically repressed during development, is much lower than that at the ␣1 and ␣2 promoters. Thus, the mouse ␣-globin gene cluster may be regulated through moving in or out active globin gene promoters and regulatory elements of a preexisting transcription factory in the nucleus, which is maintained by the flanking clustered housekeeping genes, to activate or inactivate ␣-globin gene expression.The human genome project has revealed that there are about 32,000 protein-encoding genes, which are distributed in 22 pairs of autosomes and 2 sex chromosomes. The genomewide bioinformatic analysis of chromosomal gene expression profiles and chromosomal gene positions reveals that genes are not randomly distributed in the genome. Moreover, highly expressed genes, especially housekeeping genes, are often clustered within specific chromosomal regions (9, 25), suggesting that their chromosomal locations may be related to their transcriptional activities and inherent regulatory properties (42,44). The estimation of the total number of nascent transcripts, active polymerase molecules, and number of transcription sites within a cell suggests that many different templates may be attached in a "cloud" of loops around a site; each site, or transcription "factory," would contain approximately 30 active polymerases and associated transcripts (22). Active RNA polymerases are concentrated in these discrete "factories," where they work together on the transcription of particular groups of genes (34,35,39). However, little is known about the functional correlation between the clustered gene order and their transcription. It is also unclear how these clustered genes are spatially organized in nuclei with respect to transcription and how they, as individual transcription unit...