RRC ID 21948
著者 Kanda H, Nguyen A, Chen L, Okano H, Hariharan IK.
タイトル The Drosophila ortholog of MLL3 and MLL4, trithorax related, functions as a negative regulator of tissue growth.
ジャーナル Mol Cell Biol
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.
巻・号 33(9)
ページ 1702-10
公開日 2013-5-1
DOI 10.1128/MCB.01585-12
PII MCB.01585-12
PMID 23459941
PMC PMC3624179
MeSH Animals Cell Proliferation Cell Survival Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism DNA-Binding Proteins / metabolism* Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism Gene Expression Regulation, Developmental Histone-Lysine N-Methyltransferase / genetics* Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism Humans Methylation Mutation Receptors, Notch / metabolism Signal Transduction
IF 3.611
引用数 27
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ