Studies in Drosophila led to the discovery of two of the main classes of genes that regulate gene expression by influencing chromatin structure, namely, the trithorax group (TrG) and polycomb group (PcG) ( 3, 4). While transcription factors have been studied intensively in the context of growth control, the role of chromatin-modifying proteins is less well understood. A second layer of regulation is provided by the simultaneous recruitment of proteins that influence chromatin structure and thereby determine the accessibility of DNA for transcription ( 1, 2). Extracellular signals eventually regulate gene expression by modulating the activity of proteins that bind to specific DNA sequences and influence the recruitment of the transcriptional machinery to specific promoters. In multicellular organisms, tissue growth and cell proliferation are regulated by diffusible growth factors and by cell-cell interactions.

In contrast, Trx appears to promote cell survival. Thus, in Drosophila eye imaginal discs, Trr, likely functioning together with Utx, restricts tissue growth. 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. 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. trr mutant clones display markedly reduced levels of H3K4 monomethylation without obvious changes in the levels of H3K4 di- and trimethylation. 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.

Several MLL genes are mutated in human cancers, but how these proteins regulate cell proliferation is not known. MLL1 and MLL2 are most similar to trx, while ML元 and MLL4 are more closely related to trr. 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.

Cara download transcript youtube