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Asparagine Synthetase

Epigenetic changes in the repression and induction of asparagine synthetase in human leukemic cell lines

Leukemia volume 19, pages 420–426 (2005)Cite this article

A Corrigendum to this article was published on 24 May 2005

Abstract

In common with certain other lymphoid neoplasms, cells of the human lymphocytic leukemia lines 1873 and 1929 are asparagine (ASN) auxotrophs. Asparagine synthetase (ASY), which is a housekeeping gene, is repressed and the promoting region of the gene is highly methylated. We now demonstrate in these cells multiple levels in control of the expression of this gene, in a system of cocultivation with macrophages and other cell types. In this system, mediated by cell-to-cell contact, ASY becomes expressed by the leukemic cells and they become prototrophic. Demethylation of ASY occurs; it follows expression and is permanent over multiple cell generations, but the cells return to auxotrophy with rapid repression of ASY on removal from cell contact. With ASY expression, the associated histone H3 at lysine position 9 (H3K9) becomes acetylated and H3K4, methylated. In contrast to other systems, H3K9 methylation does not characterize the repressed state. The changes leading from repression to induction of ASY and demethylation parallel the physiological changes specific to functional maturation of normal lymphoid precursors. The lability of expression of ASY has potential significance in determining the sensitivity of leukemic cells to L-asparaginase.

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Authors and Affiliations

  1. Department of Pathology, North Shore University Hospital, Manhasset, NY, USA

    Y Ding, Z Li & J D Broome

  2. New York University School of Medicine, New York, NY, USA

    Y Ding, Z Li & J D Broome

Authors
  1. Y Ding
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  2. Z Li
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  3. J D Broome
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Correspondence to J D Broome.

Additional information

This paper is written in remembrance of Dr John G Kidd (1908–1991).

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Ding, Y., Li, Z. & Broome, J. Epigenetic changes in the repression and induction of asparagine synthetase in human leukemic cell lines. Leukemia 19, 420–426 (2005). https://doi.org/10.1038/sj.leu.2403639

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