title: Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei.
abstract: 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.
authors.affiliation: Ludwig Maximilians University Munich, Department of Biology II, 80336 Munich, Germany. Dani.Zink@lrz.uni-muenchen.de
authors.forename: Daniele
authors.initials: D
authors.lastname: Zink
authors.forename: Margarida D
authors.initials: MD
authors.lastname: Amaral
authors.forename: Andreas
authors.initials: A
authors.lastname: Englmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Lang
authors.forename: Luka A
authors.initials: LA
authors.lastname: Clarke
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudolph
authors.forename: Felix
authors.initials: F
authors.lastname: Alt
authors.forename: Kathrin
authors.initials: K
authors.lastname: Luther
authors.forename: Carla
authors.initials: C
authors.lastname: Braz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sadoni
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenecker
authors.forename: Dirk
authors.initials: D
authors.lastname: Schindelhauer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D022041:Euchromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D026901:Membrane Transport Proteins; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: C467810:ASZ1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C505032:CFTR protein, human; C442860:CTTNBP2 protein, human; D002352:Carrier Proteins; D002843:Chromatin; D022041:Euchromatin; D006570:Heterochromatin; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator