title: Distinct mechanisms of transcriptional pausing orchestrated by GAGA factor and M1BP, a novel transcription factor.
abstract: Thousands of genes in Drosophila have Pol II paused in the promoter proximal region. Almost half of these genes are associated with either GAGA factor (GAF) or a newly discovered factor we call M1BP. Although both factors dictate the association of Pol II at their target promoters, they are nearly mutually exclusive on the genome and mediate different mechanisms of regulation. High-resolution mapping of Pol II using permanganate-ChIP-seq indicates that pausing on M1BP genes is transient and could involve the +1 nucleosome. In contrast, pausing on GAF genes is much stronger and largely independent of nucleosomes. Distinct regulatory mechanisms are reflected by transcriptional plasticity: M1BP genes are constitutively expressed throughout development while GAF genes exhibit much greater developmental specificity. M1BP binds a core promoter element called Motif 1. Motif 1 potentially directs a distinct transcriptional mechanism from the canonical TATA box, which does not correlate with paused Pol II on the genomic scale. In contrast to M1BP and GAF genes, a significant portion of TATA box genes appear to be controlled at preinitiation complex formation.
authors.affiliation: Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: David S
authors.initials: DS
authors.lastname: Gilmour
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D009707:Nucleosomes / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D016385:TATA Box / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C583285:M1BP protein, Drosophila; D009707:Nucleosomes; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D012319:RNA Polymerase II