An elegant model that solves this problem posits that MSL complex does not act with diverse gene-specific transcription factors to alter initiation, but rather at the elongation step of transcription common to all genes. MLE is an ATPase/helicase with double stranded RNA binding motifs that associates with the complex in an RNA dependent manner.Ī long-standing puzzle is the biochemical mechanism by which the MSL complex up regulates X-linked genes, each of which is controlled by different transcription factors. MSL1 assembles the complex via discrete docking sites for MSL2, MS元, and MOF. MS元 is a chromodomain protein implicated in MSL complex distribution to its target site. The complex contains the histone modifying enzymes MOF (H4K16ac) and MSL2 (H2BK34ub). This is accomplished by the MSL complex, which consists of at least five proteins and two noncoding roX (RNA on X) RNAs. To equalize the expression of the X-linked genes between XY males and XX females, the single X-chromosome in males is hypertranscribed a modest, but essential ∼1.4–1.8 fold. We find that the dosage compensation complex genetically and physically interacts with SPT5 on actively transcribed genes providing direct molecular support for the elongation model of dosage compensation.ĭrosophila dosage compensation is widely used as a model system to investigate how transcription is regulated by large scale chromatin modifications. SPT5 closes the RNA polymerase II clamp around the DNA template to prevent pausing or premature termination. We performed a genetic screen for mutations that subtly reduce dosage compensation and recovered mutations in the Spt5 gene that encodes a universally conserved elongation factor. An alternative model proposed that dosage compensation instead acted at some step of transcription elongation common to all genes. It had been difficult to imagine how the MSL dosage compensation complex could impose a modest, but essential, ∼two-fold increase by interacting with hundreds of different factors that control transcription initiation for such a diverse collection of genes. Drosophila males hypertranscribe most of the genes along their single X chromosome to match the output of females with two X chromosomes.
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