Chromatin reader L(3)mbt requires the Myb–MuvB/DREAM transcriptional regulatory complex for chromosomal recruitment

Significance Histone binding proteins are critical for chromosome function, and mechanisms targeting them to nucleosomes are crucial. TheDrosophila tumor suppressor L(3)mbt binds to methylated lysines of nucleosomal histones repressing gene transcription. We show that L(3)mbt chromosomal targeting requires proteins of a site-specific DNA binding complex [Myb–MuvB (MMB)/DREAM] and Mip120, an MMB/DREAM core component, is critical for recruitment. Surprisingly, chromosome association of L(3)mbt is insufficient for repression, as other MMB/DREAM members are required for L(3)mbt-mediated repression but not its chromosome targeting. Loss ofl (3 )mbt leads to lethal malignant brain tumors. We discuss our findings in the context of complex mechanisms where specific genes activated by loss ofl (3 )mbt may help tumor progression, whereas deletion of MMB genes may suppress this phenotype.