Phosphorylation of histone H3 at Ser10 facilitates RNA polymerase II release from promoter-proximal pausing in Drosophila.

Abstract

The Drosophila JIL-1 kinase is known to phosphorylate histone H3 at Ser10 (H3S10) during interphase. This modification is associated with transcriptional activation, but its function is not well understood. Here we present evidence suggesting that JIl-1-mediated H3S10 phosphorylation is dependent on chromatin remodeling by the brahma complex and is required during early transcription elongation to release RNA polymerase II (Pol II) from promoter-proximal pausing. JIL-1 localizes to transcriptionally active regions and is required for activation of the E75A ecdysone-responsive and hsp70 heat-shock genes. The heat-shock transcription factor, the promoter-paused form of Pol II (Pol IIo(ser5)), and the pausing factor DSIF (DRB sensitivity-inducing factor) are still present at the hsp70 loci in JIL-1-null mutants, whereas levels of the elongating form of Pol II (Pol IIo(ser2)) and the P-TEFb kinase are dramatically reduced. These observations suggest that phosphorylation of H3S10 takes place after transcription initiation but prior to recruitment of P-TEFb and productive elongation. Western analyses of global levels of both forms of Pol II further suggest that JIL-1 plays a general role in early elongation of a broad range of genes. Taken together, the results introduce H3S10 phosphorylation by JIL-1 as a hallmark of early transcription elongation in Drosophila.

• Authors: M Soledad Ivaldi, Caline S Karam, Victor G Corces
• Journal: Genes & development (Genes Dev) Vol. 21 Issue 21 Pg. 2818-31 (Nov 01 2007) ISSN: 0890-9369 [Print] United States
• PMID: 17942706 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cell Cycle Proteins
• DNA-Binding Proteins
• Drosophila Proteins
• Heat Shock Transcription Factors
• Heat-Shock Proteins
• Histones
• Homeodomain Proteins
• Hsf protein, Drosophila
• Trans-Activators
• Transcription Factors
• brm protein, Drosophila
• Ecdysone
• Serine
• Protein Kinases
• Positive Transcriptional Elongation Factor B
• JIL-1 protein, Drosophila
• Protein Serine-Threonine Kinases
• RNA Polymerase II
• DNA Helicases
• kis protein, Drosophila

Topics

• Animals
• Animals, Genetically Modified
• Cell Cycle Proteins (metabolism)
• Chromatin Assembly and Disassembly (physiology)
• Chromosomes (metabolism)
• DNA Helicases (genetics)
• DNA-Binding Proteins (metabolism)
• Drosophila (genetics, metabolism)
• Drosophila Proteins (genetics, metabolism)
• Ecdysone (physiology)
• Gene Expression Regulation
• Heat Shock Transcription Factors
• Heat-Shock Proteins (genetics)
• Histones (chemistry, metabolism)
• Homeodomain Proteins (genetics)
• Models, Biological
• Phosphorylation
• Positive Transcriptional Elongation Factor B (metabolism)
• Promoter Regions, Genetic
• Protein Kinases (metabolism, physiology)
• Protein Serine-Threonine Kinases (metabolism)
• RNA Polymerase II (metabolism, physiology)
• Serine (metabolism)
• Trans-Activators (metabolism)
• Transcription Factors (metabolism)
• Transcription, Genetic (genetics)