Efficient Release from Promoter-Proximal Stall Sites Requires Transcript Cleavage Factor TFIIS

Adelman, Karen; Marr, Michael T.; Werner, Janis; Saunders, Abbie; Ni, Zhuoyu; Andrulis, Erik D.; Lis, John T.

doi:10.1016/j.molcel.2004.11.028

Cited by 151 publications

(140 citation statements)

References 49 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…This activity is critical for the efficient escape of RNAPII from promoter-proximal pause sites at the drosophila Hsp70 gene. 17 RNAPII can backtrack as far as 18-20 bases, 18 which is similar to the size of TSSa-RNAs. TFIIS reactivation of these complexes would then release a RNA with a 5'-monophosphate, making them detectable in the short RNA cloning procedure used by Seila et al Validation of several TSSa-RNA populations by northern blot, shows that sequenced TSSa-RNAs are a subset of a RNA population ranging from 20-90 bases in length.…”

Section: General Features Of Transcriptionmentioning

confidence: 85%

Divergent transcription: A new feature of active promoters

Seila¹,

Core²,

Lis³

et al. 2009

Cell Cycle

Self Cite

169

164

View full text Add to dashboard Cite

Section: General Features Of Transcriptionmentioning

confidence: 85%

Divergent transcription: A new feature of active promoters

Seila¹,

Core²,

Lis³

et al. 2009

Cell Cycle

Self Cite

169

164

View full text Add to dashboard Cite

“…However, the more general term of 'stalled' is also very useful 8,9 , especially because these populations of promoter-proximal Pol II will probably contain an equilibrium mix of both paused and arrested Pol II 29 . Nuclear run-on assays are a key technique used to define the state of Pol II.…”

Section: Box 1 J Pausing and Stallingmentioning

confidence: 99%

“…In contrast, DSIF remains associated with productively elongating Pol II and is thought to have a positive role after escape from the pause 2,28 . Paused polymerases are susceptible to backtracking, and the presence of elongation factor TFIIS at the pause region in vivo in Drosophila may stimulate the intrinsic RNA cleavage activity of Pol II to create a new RNA 39 end in the active site, and thereby maintain a population of elongationally competent complexes 29 .…”

Section: Molecular Imaging Of Proteins On Genes In Vivomentioning

confidence: 99%

“…In the case of Drosophila Hsp70, short transcripts do not accumulate, although some fraction of transcripts fail to efficiently elongate in run-on assays and are likely to be back-tracked and arrested. However, TFIIS is also present at the promoter and may allow these arrested Pol II complexes to be in dynamic equilibrium with elongationally competent paused complexes 2,29 . For some genes, Pol II shows only fractional promoter occupancy-less than one Pol II per promoter.…”

Section: Questions and Future Prospectsmentioning

confidence: 99%

See 1 more Smart Citation

Imaging Drosophila gene activation and polymerase pausing in vivo

Lis

2007

Nature

Self Cite

View full text Add to dashboard Cite

Since the early 1960s, imaging studies of Drosophila sp. polytene chromosomes have provided unique views of gene transcription in vivo. The dramatic changes in chromatin structure that accompany gene activation can be visualized as chromosome puffs. Now, live-cell imaging techniques coupled with protein-DNA crosslinking assays on a genome-wide scale allow more detailed mechanistic questions to be addressed and are prompting the re-evaluation of models of transcription regulation in both Drosophila and mammals.D etermining the complete genome sequence of humans, Drosophila and other model higher eukaryotes was an important step in cataloguing the complete code that programmes the development and maintenance of multicellular organisms. A critical challenge that remains is to determine in molecular terms how this code is read and regulated in higher eukaryotes 1 . The regulation of transcription of the genome is a major mode by which an organism controls both its homeostasis and development. This regulation is executed mainly through the interactions of a plethora of transcription factor proteins and RNAs with each other and with DNA and associated histones 2 . These interactions then dictate when, where, and to what level specific genes are transcribed. Although biochemical and genetic approaches have identified many of the macromolecular players and their activities, a mechanistic understanding of how they operate in gene regulation can be guided and tested by direct imaging of these molecular interactions and the resulting biochemical processes in living cells.Two developments in the imaging of transcription factors at specific endogenous gene loci in vivo are providing new views of transcription mechanisms and regulation. One, currently specific to Drosophila, makes use of state-of-the-art optics combined with the natural amplification of signals in tissue containing polytene chromosomes, allowing investigation of molecular interactions and dynamics at specific loci in real time in living nuclei 3 . The other, although having a history in Drosophila 4-6 , is species-general and uses crosslinking in vivo-that is, chromatin immunoprecipitation (ChIP) assays and variants thereof-to produce a 'molecular image' of specific protein interactions and chromatin modifications with particular DNA sequences in the genome 7 . Here I describe how these optical and molecular imaging approaches are providing new insights into transcription and the rate-limiting steps in its regulation in multicellular organisms. In particular, recent genome-wide ChIP assays in Drosophila 8,9 and mammals 10 support a paradigm shift in gene regulation by indicating that control of transcription elongation by RNA polymerase II (Pol II) in a promoter-proximal pausing model (Box 1), rather than control of the recruitment or initiation of Pol II, is the rate-limiting step for a large fraction of highly regulated genes. Early insights from spread polytene nucleiOver the past several decades, Drosophila has provided extraordinary views of chromosome s...

show abstract

“…Both histone phosphorylation and acetylation coincide with the recruitment of elongation factors, such as Spt6, to the Pol II complex (Andrulis et al 2000). Elongation proteins, along with TFIIS, promote Pol II release from the promoter and productive polymerization of stress-induced transcripts during the duration of the heat shock (Adelman et al 2005). In addition, chromatin-bound poly(ADP-ribose) polymerase (PARP) at heat-shock response loci is modified with long poly(ADP-ribose) chains upon induction, and this process is essential for chromatin loosening and transcript production .…”

mentioning

confidence: 99%

The Drosophila P68 RNA helicase regulates transcriptional deactivation by promoting RNA release from chromatin

Spradling¹

2006

Genes Dev.

View full text Add to dashboard Cite

Terminating a gene's activity requires that pre-existing transcripts be matured or destroyed and that the local chromatin structure be returned to an inactive configuration. Here we show that the Drosophila homolog of the mammalian P68 RNA helicase plays a novel role in RNA export and gene deactivation. p68 mutations phenotypically resemble mutations in small bristles (sbr), the Drosophila homolog of the human mRNA export factor NXF1. Full-length hsp70 mRNA accumulates in the nucleus near its sites of transcription following heat shock of p68 homozygotes, and hsp70 gene shutdown is delayed. Unstressed mutant larvae show similar defects in transcript accumulation and gene repression at diverse loci, and we find that p68 mutations are allelic to Lighten-up, a known suppressor of position effect variegation. Our observations reveal a strong connection between transcript clearance and gene repression. P68 may be needed to rapidly remove transcripts from a gene before its activity can be shut down and its chromatin reset to an inactive state.

show abstract

Efficient Release from Promoter-Proximal Stall Sites Requires Transcript Cleavage Factor TFIIS

Cited by 151 publications

References 49 publications

Divergent transcription: A new feature of active promoters

Divergent transcription: A new feature of active promoters

Imaging Drosophila gene activation and polymerase pausing in vivo

The Drosophila P68 RNA helicase regulates transcriptional deactivation by promoting RNA release from chromatin

Contact Info

Product

Resources

About