X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation.
Among organisms with chromosome-based mechanisms of sex determination, failure to equalize expression of X-linked genes between the sexes is typically lethal. In C. elegans, XX hermaphrodites halve transcription from each X chromosome to match the output of XO males. Here, we mapped the binding location of the condensin homolog DPY-27 and the zinc finger protein SDC-3, two components of the C. elegans dosage compensation complex (DCC). We observed strong foci of DCC binding on X, surrounded by broader regions of localization. Binding foci, but not adjacent regions of localization, were distinguished by clusters of a 10-bp DNA motif, suggesting a recruitment-and-spreading mechanism for X recognition. The DCC was preferentially bound upstream of genes, suggesting modulation of transcriptional initiation and polymerase-coupled spreading. Stronger DCC binding upstream of genes with high transcriptional activity indicated a mechanism for tuning DCC activity at specific loci. These data aid in understanding how proteins involved in higher-order chromosome dynamics can regulate transcription at individual loci.
Ercan
Sevinc
S
Department of Biology and Carolina Center for the Genome Sciences, 202 Fordham Hall, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280, USA.
Giresi
Paul G
PG
Whittle
Christina M
CM
Zhang
Xinmin
X
Green
Roland D
RD
Lieb
Jason D
JD
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D024363:Transcription Initiation Site; D014960:X Chromosome / Q000378:metabolism; D049951:X Chromosome Inactivation