Mutations in the Transcription Elongation Factor SPT5 Disrupt a Reporter for Dosage Compensation in Drosophila

<div><p>In <em>Drosophila</em>, the MSL (Male Specific Lethal) complex up regulates transcription of active genes on the single male X-chromosome to equalize gene expression between sexes. One model argues that the MSL complex acts upon the elongation step of transcription rather than initiation. In an unbiased forward genetic screen for new factors required for dosage compensation, we found that mutations in the universally conserved transcription elongation factor <em>Spt5</em> lower MSL complex dependent expression from the <em>miniwhite</em> reporter gene <em>in vivo</em>. We show that SPT5 interacts directly with MSL1 <em>in vitro</em> and is required downstream of MSL complex recruitment, providing the first mechanistic data corroborating the elongation model of dosage compensation.</p>