title: Chromatin reader L(3)mbt requires the Myb-MuvB/DREAM transcriptional regulatory complex for chromosomal recruitment.
abstract: Lethal malignant brain tumors (lmbt) result from the loss of the conserved transcriptional repressor l(3)mbt, in Drosophila melanogaster. Similar mutations in the human homolog L3MBTL1 correlate with some cancers. The protein's C-terminal MBT repeats bind mono and dimethylated histones in vitro, which could influence recruitment of L3MBTL1 to its target sites. The L(3)mbt chromatin targeting mechanism, however, is controversial and several studies suggest insufficiency or a minor role for histone methylation in determining the site specificity for recruitment. We report that L(3)mbt colocalizes with core members of the Myb-MuvB/DREAM (MMB/DREAM) transcriptional regulatory complex genome-wide, and that L(3)mbt-mediated repression requires this complex in salivary glands and larval brains. Loss of l(3)mbt or of MMB components through mutation cause similar spurious expression of genes, including the transposon regulatory gene piwi, in terminally differentiated cells. The DNA-binding MMB core component Mip120 (Lin54) is required for L(3)mbt recruitment to chromosomes, whereas Mip130 (Lin9) (an MMB core protein) and E2f2 (an MMB transcriptional repressor) are not, but are essential for repression. Cytolocalization experiments suggest the presence of site-specific differential composition of MMB in polytene chromosomes where some loci were bound by a Myb-containing or alternatively, an E2f2 and L(3)mbt form of the complex.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Blanchard
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and.
authors.forename: Daphne
authors.initials: D
authors.lastname: Georlette
authors.affiliation: Department of Biology, Canisius College, Buffalo, NY 14208.
authors.forename: Lisa
authors.initials: L
authors.lastname: Antoszewski
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and mbotchan@berkeley.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Botchan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D059006:Chromosomes, Insect / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D050703:E2F2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; C115434:E2f2 protein, Drosophila; D006657:Histones; D008164:Luminescent Proteins; C519699:Mip120 protein, Drosophila; C489655:Mip130 protein, Drosophila; D046912:Multiprotein Complexes; C467519:Myb protein, Drosophila; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors; C555103:l(3)mbt protein, Drosophila; D020169:Caspases; C438246:STRICA protein, Drosophila
keywords: bar coding; epigenetics; tumorigenesis