Incorporation of a loss of function SNR1 subunit led to alterations in RNA polymerase elongation and pre-mRNA splicing regulation.
Nucleosome remodeling by the is essential for regulated gene expression.
The Drosophila Brahma (Brm) SWI/SNF complex responds to ecdysone hormone signaling during development.
Loss of chromatin remodeling function is linked to developmental abnormalities and aggressive cancers.
plays a unique role in regulating target gene expression by restricting BRM-dependent nucleosome remodeling.
Changes in chromatin accessibility of hormone-regulated genes were observed with SNR1 dysfunction.
Simplified
Nucleosome remodeling catalyzed by the ATP-dependent is essential for regulated gene expression. Transcriptome profiling studies in flies and mammals identified cell cycle and hormone responsive genes as important targets of remodeling complex activities. Loss of chromatin remodeling function has been linked to developmental abnormalities and aggressive cancers. The Drosophila Brahma (Brm) SWI/SNF complex assists in reprogramming and coordinating gene expression in response to ecdysone hormone signaling at critical points during development. We used RNAi knockdown in cultured cells and transgenic flies, and conditional mutant alleles to identify unique and important functions of two conserved Brm complex core subunits, and BRM/SNF2-SWI2, on target gene regulation. Unexpectedly, we found that incorporation of a loss of function SNR1 subunit led to alterations in RNA polymerase elongation, pre-mRNA splicing regulation and chromatin accessibility of ecdysone hormone regulated genes, revealing that SNR1 functions to restrict BRM-dependent nucleosome remodeling activities downstream of the promoter region. Our results reveal critically important roles of the SNR1/SNF5 subunit and the Brm chromatin remodeling complex in transcription regulation during elongation by RNA Polymerase II and completion of pre-mRNA transcripts that are dependent on hormone signaling in late development.
Key numbers
79-fold
Increase in spliced product
Measured in developmental stages where transcripts are detected.
6-fold
Reduction in 3′ transcript
Observed in early pupae with RNAi depletion of NELF.
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