A Sequence Motif within Chromatin Entry Sites Directs MSL Establishment on the Drosophila X Chromosome

• Published in: Cell Vol. 134; no. 4; pp. 599 - 609
• Main Authors: Alekseyenko, Artyom A., Peng, Shouyong, Larschan, Erica, Gorchakov, Andrey A., Lee, Ok-Kyung, Kharchenko, Peter, McGrath, Sean D., Wang, Charlotte I., Mardis, Elaine R., Park, Peter J., Kuroda, Mitzi I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.08.2008
• Subjects: Animals; Base Sequence; Chromatin Immunoprecipitation; DEVBIO; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Female; Male; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; PROTEINS; RNA; Transcription Factors - genetics; Transcription Factors - metabolism; X Chromosome - genetics; X Chromosome - metabolism; RNA; PROTEINS; DEVBIO
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2008.06.033

The Drosophila MSL complex associates with active genes specifically on the male X chromosome to acetylate histone H4 at lysine 16 and increase expression approximately 2-fold. To date, no DNA sequence has been discovered to explain the specificity of MSL binding. We hypothesized that sequence-specific targeting occurs at “chromatin entry sites,” but the majority of sites are sequence independent. Here we characterize 150 potential entry sites by ChIP-chip and ChIP-seq and discover a GA-rich MSL recognition element (MRE). The motif is only slightly enriched on the X chromosome (∼2-fold), but this is doubled when considering its preferential location within or 3′ to active genes (>4-fold enrichment). When inserted on an autosome, a newly identified site can direct local MSL spreading to flanking active genes. These results provide strong evidence for both sequence-dependent and -independent steps in MSL targeting of dosage compensation to the male X chromosome.