The essential process of dosage compensation equalizes X-chromosome gene expression between C. elegans XO males and XX hermaphrodites through a dosage compensation complex (DCC) that resembles condensin. The DCC binds to both X chromosomes of hermaphrodites to repress transcription by half. Here we show that post-translational modification by the SUMO conjugation pathway is essential for sex-specific assembly of the DCC onto X. Depletion of the SUMO peptide in vivo severely disrupts binding of particular DCC subunits and causes changes in X-linked gene expression similar to those caused by disrupting genes encoding DCC subunits. Three DCC subunits are themselves SUMOylated, and depletion of SUMO preferentially reduces their binding to X, suggesting that SUMOylation of DCC subunits is essential for robust association with X. DCC SUMOylation is triggered by the signal that initiates DCC assembly onto X. The initial step of assembly--binding of X-targeting factors to recruitment sites on X (rex sites)--is independent of SUMOylation, but robust binding of the complete complex requires SUMOylation. SUMOylated DCC subunits are enriched at rex sites, and SUMOylation enhances interactions between X-targeting factors and condensin subunits that facilitate DCC binding beyond the low level achieved without SUMOylation. DCC subunits also participate in condensin complexes essential for chromosome segregation, but their SUMOylation occurs only in the context of the DCC. Our results reinforce a newly emerging theme in which multiple proteins of a complex are SUMOylated in response to a specific stimulus, leading to accelerated complex formation and enhanced function.
We used microarray analysis to further our understanding of the mode of action of the well know caloric restriction mimetic rapamycin and the compound Allantoin first studied in the context of aging in this study. His work helps build on our understanding of potential caloric restriction mimetics predicted from our bioinformatic aproach of quering the Connectivity Map, a database of drug-induced gene expression profiles, using the transcriptional profile of CR to identify drugs that induce a similar or opposite gene expression profile.
Illumina HiSeq 2000 paired end sequencing; Illumina sequencing of C. elegans dauer entry daf-2(el370) sample 1-1 DauerEntryDAF2-1-1 polyA+ 101bp PE RNAseq random fragment library RW0001
Illumina HiSeq 2000 paired end sequencing; Illumina sequencing of C. elegans dauer entry daf-2(el370) sample 1-1 DauerEntryDAF2-1-1 polyA+ 100bp SE RNAseq random fragment library RW0001
Illumina HiSeq 2000 paired end sequencing; Illumina sequencing of C. elegans dauer entry daf-2(el370) sample 1-1 DauerEntryDAF2-1-1 polyA+ 100bp PE RNAseq random fragment library RW0001
Illumina HiSeq 2000 paired end sequencing; Illumina sequencing of C. elegans dauer entry daf-2(el370) sample 1-1 DauerEntryDAF2-1-1 polyA+ 101bp SE RNAseq random fragment library RW0001
We showed that KLF-1 is needed for longevity of isp-1(qm150);ctb-1(qm189) mutant specifically in adulthood. We aimed to determine the expression changes that occur specifically upon adulthood klf-1 RNAi compared to developmental RNAi that did not affect the lifespan of isp-1(qm150);ctb-1(qm189) mutant.