Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development

Robin D. Hanson, Jay Hess, Benjamin D. Yu, Patricia Ernst, Maarten Van Lohuizen, Anton Berns, Nathalie M T Van Der Lugt, Cooduvalli S. Shashikant, Frank H. Ruddle, Masao Seto, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

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Abstract

Control of cell identity during development is specified in large part by the unique expression patterns of multiple homeobox-containing (Hox) genes in specific segments of an embryo. Trithorax and Polycomb-group (Trx-G and Pc-G) proteins in Drosophila maintain Hox expression or repression, respectively. Mixed lineage leukemia (MLL) is frequently involved in chromosomal translocations associated with acute leukemia and is the one established mammalian homologue of Trx. Bmi-1 was first identified as a collaborator in c-myc-induced murine lymphomagenesis and is homologous to the Drosophila Pc-G member Posterior sex combs. Here, we note the axial-skeletal transformations and altered Hox expression patterns of MII-deficient and Bmi- 1-deficient mice were normalized when both MII and Bmi-1 were deleted, demonstrating their antagonistic role in determining segmental identity. Embryonic fibroblasts from MII-deficient compared with Bmi-1-deficient mice demonstrate reciprocal regulation of Hox genes as well as an integrated Hoxc8-lacZ reporter construct. Reexpression of MLL was able to overcome repression, rescuing expression of Hoxc8-lacZ in MII-deficient cells. Consistent with this, MLL and BMI-I display discrete subnuclear colocalization. Although Drosophila Pc-G and Trx-G members have been shown to maintain a previously established transcriptional pattern, we demonstrate that MLL can also dynamically regulate a target Hox gene.

Original languageEnglish (US)
Pages (from-to)14372-14377
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number25
DOIs
StatePublished - Dec 7 1999
Externally publishedYes

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Homeobox Genes
Leukemia
Drosophila
Comb and Wattles
Genetic Translocation
Embryonic Structures
Fibroblasts

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development. / Hanson, Robin D.; Hess, Jay; Yu, Benjamin D.; Ernst, Patricia; Van Lohuizen, Maarten; Berns, Anton; Van Der Lugt, Nathalie M T; Shashikant, Cooduvalli S.; Ruddle, Frank H.; Seto, Masao; Korsmeyer, Stanley J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 25, 07.12.1999, p. 14372-14377.

Research output: Contribution to journalArticle

Hanson, RD, Hess, J, Yu, BD, Ernst, P, Van Lohuizen, M, Berns, A, Van Der Lugt, NMT, Shashikant, CS, Ruddle, FH, Seto, M & Korsmeyer, SJ 1999, 'Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 25, pp. 14372-14377. https://doi.org/10.1073/pnas.96.25.14372
Hanson, Robin D. ; Hess, Jay ; Yu, Benjamin D. ; Ernst, Patricia ; Van Lohuizen, Maarten ; Berns, Anton ; Van Der Lugt, Nathalie M T ; Shashikant, Cooduvalli S. ; Ruddle, Frank H. ; Seto, Masao ; Korsmeyer, Stanley J. / Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 25. pp. 14372-14377.
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