We investigated in different human cell types nuclear positioning and transcriptional regulation of the functionally unrelated genes GASZ, CFTR, and CORTBP2, mapping to adjacent loci on human chromosome 7q31. When inactive, GASZ, CFTR, and CORTBP2 preferentially associated with the nuclear periphery and with perinuclear heterochromatin, whereas in their actively transcribed states the gene loci preferentially associated with euchromatin in the nuclear interior. Adjacent genes associated simultaneously with these distinct chromatin fractions localizing at different nuclear regions, in accordance with their individual transcriptional regulation. Although the nuclear localization of CFTR changed after altering its transcription levels, the transcriptional status of CFTR was not changed by driving this gene into a different nuclear environment. This implied that the transcriptional activity affected the nuclear positioning, and not vice versa. Together, the results show that small chromosomal subregions can display highly flexible nuclear organizations that are regulated at the level of individual genes in a transcription-dependent manner.
Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei
S. Lang's present address is Max Planck Institute for Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
K. Luther's present address is Max von Pettenkofer Institute, 80336 Munich, Germany.
Abbreviations used in this paper: 3D, three-dimensional; CFTR, cystic fibrosis transmembrane conductance regulator; CORTBP2, cortactin-binding protein 2; DRB, 5,6-dichlorobenzimidazole riboside; GASZ, germ cell–specific expression, presence of ANK, SAM, and basic leucine zipper domains; H4Ac8, H4 acetylated at lysine 8; LAP2β, lamina-associated polypeptide 2β; TSA, trichostatin A.
Daniele Zink, Margarida D. Amaral, Andreas Englmann, Susanne Lang, Luka A. Clarke, Carsten Rudolph, Felix Alt, Kathrin Luther, Carla Braz, Nicolas Sadoni, Joseph Rosenecker, Dirk Schindelhauer; Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei . J Cell Biol 13 September 2004; 166 (6): 815–825. doi: https://doi.org/10.1083/jcb.200404107
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