Local gene density predicts the spatial position of genetic loci in the interphase nucleus

Andrea E. Murmann, Juntao Gao, Marissa Encinosa, Mathieu Gautier, Marcus E. Peter, Roland Eils, Peter Lichter*, Janet D. Rowley

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Specific chromosomal translocations are hallmarks of many human leukemias. The basis for these translocation events is poorly understood, but it has been assumed that spatial positioning of genes in the nucleus of hematopoietic cells is a contributing factor. Analysis of the nuclear 3D position of the gene MLL, frequently involved in chromosomal translocations and five of its translocation partners (AF4, AF6, AF9, ENL and ELL), and two control loci revealed a characteristic radial distribution pattern in all hematopoietic cells studied. Genes in areas of high local gene density were found positioned towards the nuclear center, whereas genes in regions of low gene density were detected closer to the nuclear periphery. The gene density within a 2 Mbp window was found to be a better predictor for the relative positioning of a genomic locus within the cell nucleus than the gene density of entire chromosomes. Analysis of the position of MLL, AF4, AF6 and AF9 in cell lines carrying chromosomal translocations involving these genes revealed that the position of the normal genes was different from that of the fusion genes, and this was again consistent with the changes in local gene density within a 2 Mbp window. Thus, alterations in gene density directly at translocation junctions could explain the change in the position of affected genes in leukemia cells.

Original languageEnglish (US)
Pages (from-to)14-26
Number of pages13
JournalExperimental Cell Research
Volume311
Issue number1
DOIs
StatePublished - Nov 15 2005

Keywords

  • Gene density
  • MLL
  • Nuclear organization
  • Translocation

ASJC Scopus subject areas

  • Cell Biology

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