Transcriptional repression by the Caenorhabditis elegans germ-line protein PIE-1

Batchelder, Ceri; Dunn, Melanie A.; Choy, Bob K.; Suh, Yong; Cassie, Conrad D.; Shim, Eun Yong; Shin, Tae Ho; Mello, Craig C.; Seydoux, Géraldine; Blackwell, T. Keith

doi:10.1101/gad.13.2.202

Cited by 119 publications

(123 citation statements)

References 68 publications

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“…4B) (22,23). Similar foci are normally present in the embryonic germ line, where transcription is blocked by PIE-1 (51), a global repressor that appears to act at a postinitiation step (52,53). These anti-phospho-Ser-5 foci depend upon the presence of the general transcription factor TFIIB, the mediator component RGR-1, and the CTD Ser-5 kinase CDK-7 (22, 38, 54), but not upon the mRNA capping enzyme or the elongation kinase P-TEFb, which are required 2 A. Walker, P. Dufourcq, and F. Gay, unpublished observations.…”

Section: Taf-1 Required Broadly In C Elegans Transcriptionmentioning

confidence: 79%

An Extensive Requirement for Transcription Factor IID-specific TAF-1 in Caenorhabditis elegans Embryonic Transcription

Walker

Shi

Blackwell

2004

Journal of Biological Chemistry

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The general transcription factor TFIID sets the mRNA start site and consists of TATA-binding protein and associated factors (TAF II s), some of which are also present in SPT-ADA-GCN5 (SAGA)-related complexes. In yeast, results of multiple studies indicate that TFIID-specific TAF II s are not required for the transcription of most genes, implying that intact TFIID may have a surprisingly specialized role in transcription. Relatively little is known about how TAF II s contribute to metazoan transcription in vivo, especially at developmental and tissuespecific genes. Previously, we investigated functions of four shared TFIID/SAGA TAF II s in Caenorhabditis elegans. Whereas TAF-4 was required for essentially all embryonic transcription, TAF-5, TAF-9, and TAF-10 were dispensable at multiple developmental and other metazoan-specific promoters. Here we show evidence that in C. elegans embryos transcription of most genes requires TFIID-specific TAF-1. TAF-1 is not as universally required as TAF-4, but it is essential for a greater proportion of transcription than TAF-5, -9, or -10 and is important for transcription of many developmental and other metazoan-specific genes. TAF-2, which binds core promoters with TAF-1, appears to be required for a similarly substantial proportion of transcription. C. elegans TAF-1 overlaps functionally with the coactivator p300/ CBP (CBP-1), and at some genes it is required along with the TBP-like protein TLF(TRF2). We conclude that during C. elegans embryogenesis TAF-1 and TFIID have broad roles in transcription and development and that TFIID and TLF may act together at certain promoters. Our findings imply that in metazoans TFIID may be of widespread importance for transcription and for expression of tissue-specific genes.Eukaryotic mRNA transcription involves formation of a preinitiation complex (PIC) 1 at the core promoter, which directs initiation. The PIC includes a set of general transcription factors (TFIIA, B, D, E, F, and H) and a mediator complex, along with RNA polymerase II (pol II) (1, 2). In Saccharomyces cerevisiae many PIC components have surprisingly specific roles at particular gene subsets (3, 4). Much less is known about how individual PIC components contribute to transcription regulation in metazoans, which have evolved a greater complexity of stage-and tissue-specific gene control and additional genes that are not present in yeast.The general transcription factor TFIID is of particular interest because it establishes the start site and provides enzymatic activities that may regulate transcription (5, 6). TFIID is comprised of the TATA-binding protein (TBP) along with ϳ14 TBP-associated factors (TAF II s). TAF II s interact with core promoter elements and contact a diverse array of upstream transactivators (5-8). TAF-1 and TAF-2 together bind directly to the initiator (Inr) element, which encompasses the start site (9). TAF-1, the largest TAF II , is also necessary for TFIID stability and possesses histone acetyltransferase, kinase, and ubiquitin conjugating activitie...

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Section: Taf-1 Required Broadly In C Elegans Transcriptionmentioning

confidence: 79%

An Extensive Requirement for Transcription Factor IID-specific TAF-1 in Caenorhabditis elegans Embryonic Transcription

Walker

Shi

Blackwell

2004

Journal of Biological Chemistry

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“…In addition, extensive developmental defects may stem from the derepression of P-TEFb, which could in turn promote expression of otherwise silent developmental control genes that may contain paused RNAPII molecules. Importantly, transient and global inhibition of P-TEFb has been proposed to be essential for maintaining germ cell identity in C. elegans (30,31) and Drosophila (32), and transcription elongation controls cell fate specification in the Drosophila embryo (33). We therefore speculate that 7SK snRNP disintegration would lead to inappropriate differentiations and loss of identities of germ cells and multiple somatic cell lineages, causing developmental defects observed here.…”

Section: Discussionmentioning

confidence: 91%

7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development

Barborič

Lenasi

Chen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

150

176

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Eukaryotic gene expression is commonly controlled at the level of RNA polymerase II (RNAPII) pausing subsequent to transcription initiation. Transcription elongation is stimulated by the positive transcription elongation factor b (P-TEFb) kinase, which is suppressed within the 7SK small nuclear ribonucleoprotein (7SK snRNP). However, the biogenesis and functional significance of 7SK snRNP remain poorly understood. Here, we report that LARP7, BCDIN3, and the noncoding 7SK small nuclear RNA (7SK) are vital for the formation and stability of a cell stress-resistant core 7SK snRNP. Our functional studies demonstrate that 7SK snRNP is not only critical for controlling transcription elongation, but also for regulating alternative splicing of pre-mRNAs. Using a transient expression splicing assay, we find that 7SK snRNP disintegration promotes inclusion of an alternative exon via the increased occupancy of P-TEFb, Ser2-phosphorylated (Ser2-P) RNAPII, and the splicing factor SF2/ASF at the minigene. Importantly, knockdown of larp7 or bcdin3 orthologues in zebrafish embryos destabilizes 7SK and causes severe developmental defects and aberrant splicing of analyzed transcripts. These findings reveal a key role for P-TEFb in coupling transcription elongation with alternative splicing, and suggest that maintaining core 7SK snRNP is essential for vertebrate development.C hallenging the once predominantly held view that RNA polymerase II (RNAPII) recruitment to promoters is the rate-limiting event in regulating eukaryotic transcription, several recent studies indicate that RNAPII pauses subsequently to transcription initiation at a large number of genes in Drosophila and in several cell lineages in humans (1). A paradigm for this type of control is the regulation of HIV-1 transcription, which is paused because of concerted actions of the negative transcription elongation factors (N-TEFs) (1, 2). The block is reversed by the positive transcription elongation factor b (P-TEFb), consisting of a heterodimer between the cyclin-dependent kinase 9 (Cdk9) and one of the four C-type cyclins (CycT1/T2a(b)/K) (2), which phosphorylates Ser2 within the multiple heptapeptide repeats YSPTSPS of the carboxy-terminal domain (CTD) of the Rpb1 subunit of RNAPII, as well as components of N-TEFs. Of note, P-TEFb is critical for expressing early embryonic genes in C. elegans (3), and experiments in yeast and Drosophila demonstrate that it is also vital for proper 3Ј end pre-mRNA processing (4, 5). Thus, regulating transcription elongation is a key checkpoint for modulating eukaryotic gene expression.P-TEFb exists in 2 mutually exclusive complexes that differ in their kinase activity (2). A transcriptionally inactive complex [referred to herein as 7SK small nuclear ribonucleoprotein (7SK snRNP)] contains P-TEFb, hexamethylene bisacetamide-induced protein (HEXIM) 1 (HEXIM1) and/or HEXIM2, the noncoding 7SK small nuclear RNA (7SK) and the La-related protein 7 (LARP7) (6-12). Therein, 7SK is a molecular scaffold, which binds HEXIM1, HEXIM2, and LARP7 d...

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“…When PIE-1 is present, P-TEFb is thought to be recruited away from RNAPII, preventing phosphorylation of Ser2 and inhibiting transcriptional elongation (Figure 2b). 37,38 In addition, PIE-1 uses a different but still undefined mechanism to prevent phosphorylation of serine 5 of the CTD, thereby inhibiting PREINITIATION COMPLEX formation and transcriptional initiation. 39 Transcription is repressed in the early D. melanogaster germline by a mechanistically similar but independently derived mechanism.…”

Section: Specification Of the Germlinementioning

confidence: 99%

Genetics of germ cell development

2012

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| The germ line represents a continuous cellular link between generations and between species, but the germ cells themselves develop in a specialized, organism-specific context. The three most common animal model organisms, C. elegans, Drosophila, and mouse, display striking similarities as well as major differences in the means by which they control germ cell development.Comparison of the germ cells of these three organisms sheds light not only on universal aspects of germline regulation, but also on control of the pluripotent state in vivo and on the earliest steps of embryogenesis. Taking a broad perspective, we will follow the germ cells from specification in the early embryo, through gametogenesis, to fertilization, and highlight themes from the comparison of three alternative strategies for navigating the fundamental cycle of sexual reproduction.

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Transcriptional repression by the Caenorhabditis elegans germ-line protein PIE-1

Cited by 119 publications

References 68 publications

An Extensive Requirement for Transcription Factor IID-specific TAF-1 in Caenorhabditis elegans Embryonic Transcription

An Extensive Requirement for Transcription Factor IID-specific TAF-1 in Caenorhabditis elegans Embryonic Transcription

7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development

Genetics of germ cell development

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