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T Neoplasias

The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells

Leukemia volume 20, pages 304–312 (2006)Cite this article

Abstract

TLX1/HOX11, a DNA-binding homeodomain protein, was originally identified by virtue of its aberrant expression in T-cell leukemia and subsequently found to be crucial for normal spleen development. The precise mechanism of TLX1 function remains poorly understood, although it is known that it can act as both a transcriptional activator and repressor and can downregulate the Aldh1a1 gene in embryonic mouse spleen. Using a whole-genome PCR approach, we show here that TLX1 protein directly interacts with pericentromeric human satellite 2 DNA sequences. Such DNA is known to localize to heterochromatin, which among other roles has been implicated in gene silencing. The interaction was confirmed in vitro and in vivo by gel retardation and chromatin immunoprecipitation assays involving satellite 2 DNA, which contained sequences resembling TLX1 binding sites. Using immunofluorescence microscopy, TLX1 demonstrated a punctate pattern of staining in the nuclei of leukemic T-cells (ALL-SIL). Double labelling indicated that TLX1 colocalized with the centromeric protein CENP-B, demonstrating that the TLX1 foci corresponded to clusters of centromeric DNA. The novel interaction of TLX1 with constitutive heterochromatin adds an additional level of complexity to the intracellular functions of this transcriptional regulator and may have relevance to its roles in transcriptional repression and T-cell immortalization.

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Acknowledgements

We thank S Harris and K Johnson for providing a detailed whole genome PCR protocol; J Ford, J Blinco, D Berryman, M Bassami, P Dallas and J Murphy for their technical advice and assistance. This work was supported by grants from the Australian National Health and Medical Research Council (NHMRC; Grant No. 110236) and Murdoch University. MH was the recipient of a PhD scholarship from the Iranian Ministry of Health and Medical Education KLR was supported by an Australian Postgraduate Award.

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  1. M Heidari

    Present address: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran

  2. K L Rice

    Present address: Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA

Authors and Affiliations

  1. Division of Health Sciences, School of Veterinary and Biomedical Sciences, Murdoch University, Perth, WA, Australia

    M Heidari, K L Rice, J K Phillips & W K Greene

  2. Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, Perth, WA, Australia

    U R Kees

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Correspondence to W K Greene.

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Heidari, M., Rice, K., Phillips, J. et al. The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells. Leukemia 20, 304–312 (2006). https://doi.org/10.1038/sj.leu.2404071

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