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Citation
Kanda, H., Nguyen, A., Chen, L., Okano, H., Hariharan, I.K. (2013). The Drosophila Ortholog of MLL3 and MLL4, trithorax related, Functions as a Negative Regulator of Tissue Growth.  Mol. Cell. Biol. 33(9): 1702--1710.
FlyBase ID
FBrf0221244
Publication Type
Research paper
Abstract

The human MLL genes (MLL1 to MLL4) and their Drosophila orthologs, trithorax (trx) and trithorax related (trr), encode proteins capable of methylating histone H3 on lysine 4. MLL1 and MLL2 are most similar to trx, while MLL3 and MLL4 are more closely related to trr. Several MLL genes are mutated in human cancers, but how these proteins regulate cell proliferation is not known. Here we show that trr mutant cells have a growth advantage over their wild-type neighbors and display changes in the levels of multiple proteins that regulate growth and cell division, including Notch, Capicua, and cyclin B. trr mutant clones display markedly reduced levels of H3K4 monomethylation without obvious changes in the levels of H3K4 di- and trimethylation. The trr mutant phenotype resembles that of Utx, which encodes a H3K27 demethylase, consistent with the observation that Trr and Utx are found in the same protein complex. In contrast to the overgrowth displayed by trr mutant tissue, trx clones are underrepresented, express low levels of the antiapoptotic protein Diap1, and exhibit only modest changes in global levels of H3K4 methylation. Thus, in Drosophila eye imaginal discs, Trr, likely functioning together with Utx, restricts tissue growth. In contrast, Trx appears to promote cell survival.

PubMed ID
PubMed Central ID
PMC3624179 (PMC) (EuropePMC)
Related Publication(s)
Note

Drosophila SETs Its Sights on Cancer: Trr/MLL3/4 COMPASS-Like Complexes in Development and Disease.
Morgan and Shilatifard, 2013, Mol. Cell. Biol. 33(9): 1698--1701 [FBrf0221172]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Cell. Biol.
    Title
    Molecular and Cellular Biology
    Publication Year
    1981-
    ISBN/ISSN
    0270-7306
    Data From Reference
    Alleles (9)
    Genes (11)
    Insertions (1)
    Transgenic Constructs (2)