The radial nuclear positioning of genes correlates with features of megabase-sized chromatin domains.
A nonrandom radial nuclear organization of genes has been well documented. This study provides further evidence that radial positioning depends on features of corresponding ∼1 Mbp chromatin domains (CDs), which represent the basic units of higher-order chromatin organization. We performed a quantitative three-dimensional analysis of the radial nuclear organization of three genes located on chromosome 1 in a DG75 Burkitt lymphoma-derived cell line. Quantitative real-time polymerase chain reaction revealed similar transcription levels for the three selected genes, whereas the total expression strength (TES) calculated as the sum of transcription of all genes annotated within a surrounding window of about 1 Mbp DNA differed for each region. Radial nuclear position of the studied CDs correlated with TES, i.e., the domain with the highest TES occupied the most interior position. Positions of CDs with stable TES values were stably maintained even under experimental conditions, resulting in genome-wide changes of the expression levels of many other genes. Our results strongly support the hypothesis that knowledge of the local chromatin environment is essential to predict the radial nuclear position of a gene.
Department Biologie II, Ludwig-Maximilians-Universität München, Planegg, Martinsried, Germany.
Alexandra C
AC
Kölbl
Daniela
D
Weigl
Medhanie
M
Mulaw
Tobias
T
Thormeyer
Stefan K
SK
Bohlander
Thomas
T
Cremer
Steffen
S
Dietzel
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005796:Genes / Q000235:genetics*; D006801:Humans; D021621:Imaging, Three-Dimensional; D017404:In Situ Hybridization, Fluorescence; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction