Concentration dependent chromatin states induced by the bicoid morphogen gradient

• Published in: eLife Vol. 6
• Main Authors: Hannon, Colleen E, Blythe, Shelby A, Wieschaus, Eric F
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 11-09-2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Bcd protein; Binding sites; Biochemistry; Chromatin; Chromatin - metabolism; Chromatin Immunoprecipitation; Chromosomes and Gene Expression; Deoxyribonucleic acid; Developmental Biology; DNA; DNA binding proteins; Drosophila; Drosophila - embryology; Embryonic development; Embryos; Enhancers; Gene expression; Gene Expression Regulation, Developmental; Genomes; Genomics; Homeodomain Proteins - metabolism; Insects; morphogen; Occupancy; Protein Binding; Proteins; Sequence Analysis, DNA; Trans-Activators - metabolism; Transcription (Genetics); transcription factor; Transcription factors; Wieschaus, Eric F; Canada; morphogen; stem cells; transcription factor; genes; developmental biology; chromosomes; D. melanogaster; chromatin
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.28275

In
, graded expression of the maternal transcription factor Bicoid (Bcd) provides positional information to activate target genes at different positions along the anterior-posterior axis. We have measured the genome-wide binding profile of Bcd using ChIP-seq in embryos expressing single, uniform levels of Bcd protein, and grouped Bcd-bound targets into four classes based on occupancy at different concentrations. By measuring the biochemical affinity of target enhancers in these classes in vitro and genome-wide chromatin accessibility by ATAC-seq, we found that the occupancy of target sequences by Bcd is not primarily determined by Bcd binding sites, but by chromatin context. Bcd drives an open chromatin state at a subset of its targets. Our data support a model where Bcd influences chromatin structure to gain access to concentration-sensitive targets at high concentrations, while concentration-insensitive targets are found in more accessible chromatin and are bound at low concentrations. This may be a common property of developmental transcription factors that must gain early access to their target enhancers while the chromatin state of the genome is being remodeled during large-scale transitions in the gene regulatory landscape.