A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome.
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 ( approximately 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.
Alekseyenko
Artyom A
AA
Harvard-Partners Center for Genetics and Genomics, Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Peng
Shouyong
S
Larschan
Erica
E
Gorchakov
Andrey A
AA
Lee
Ok-Kyung
OK
Kharchenko
Peter
P
McGrath
Sean D
SD
Wang
Charlotte I
CI
Mardis
Elaine R
ER
Park
Peter J
PJ
Kuroda
Mitzi I
MI
D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C094166:msl-2 protein, Drosophila; C093904:msl-3 protein, Drosophila