Drosophila ELL is associated with actively elongating RNA polymerase II on transcriptionally active sites in vivo

Gerber, Mark A.; Ma, Jiyan; Dean, Kimberly; Eissenberg, Joel C.; Shilatifard, Ali

doi:10.1093/emboj/20.21.6104

Cited by 58 publications

(58 citation statements)

References 68 publications

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“…The ELL protein has been shown to be capable of interacting with pol II and increasing its rate of transcript elongation in vitro by suppressing transient pausing by the enzyme (2,3). Consistent with a role for ELL in controlling transcript elongation in vivo, Drosophila ELL colocalizes with pol II at transcriptionally active sites on polytene chromosomes, and evidence suggests that mutations in the gene encoding Drosophila ELL may preferentially affect synthesis of long transcripts (4).…”

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confidence: 90%

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL

Kong

Banks

Shilatifard

et al. 2005

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

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In human cells, the ELL family of transcription factors includes at least three members, which are all capable of stimulating the overall rate of elongation by RNA polymerase II by suppressing transient pausing by the enzyme at many sites along DNA. In this report, we identify the ELL-associated factors (EAF)1 and EAF2 as strong positive regulators of ELL elongation activity. Our findings provide insights into the structure and function of ELL family transcription factors, and they bring to light direct roles for the EAF proteins in regulation of RNA polymerase II transcription.elongation ͉ mRNA synthesis ͉ transcription ͉ transcription factor T he gene encoding the RNA polymerase II (pol II) elongation factor eleven-nineteen lysine-rich in leukemia (ELL) was first characterized as a fusion partner of the mixed lineage leukemia (MLL) gene in the (11, 19)(q23;p13.1) translocation in acute myeloid leukemia (1). The ELL protein has been shown to be capable of interacting with pol II and increasing its rate of transcript elongation in vitro by suppressing transient pausing by the enzyme (2, 3). Consistent with a role for ELL in controlling transcript elongation in vivo, Drosophila ELL colocalizes with pol II at transcriptionally active sites on polytene chromosomes, and evidence suggests that mutations in the gene encoding Drosophila ELL may preferentially affect synthesis of long transcripts (4).In addition to ELL, human cells have two ELL paralogs, ELL2 and ELL3, which can also stimulate the rate of elongation by pol II in vitro (5, 6). ELL and ELL2 are expressed in a wide variety of tissues in humans. ELL3, on the other hand, appears to be expressed predominantly in the testis (5, 6).A variety of ELL-interacting proteins have been identified through two-hybrid screens and biochemical purifications. Two of these proteins, EAF1 and EAF2 (7,8), have been shown to colocalize with ELL in the nucleus in a stippled pattern that resembles that of Cajal bodies, structures that are enriched in factors involved in transcription and mRNA processing (9). Interestingly, Cajal bodies are disrupted in cells carrying the MLL-ELL translocation (10).Suggesting that interactions between ELL and EAF1 may contribute to the leukemic phenotype of cells expressing the MLL-ELL chimera, the C-terminal domains of EAF1 and EAF2 share similarity with AF4 and ENL, other MLL translocation partners (7,8). In addition, expression of artificial MLL-EAF1 and MLL-EAF2 chimeras can immortalize hematopoetic progenitor cells and induce the development of acute myeloid leukemia in mice (7,8). Finally, and consistent with the possibility that EAF1 and EAF2 could play a role in transcriptional regulation, their C-terminal regions function as transcriptional activation domains when fused to the GAL4 DNA binding domain (7,8).In this article, we identify the EAF1 and EAF2 proteins as positive regulators of ELL elongation activity. Our findings provide insights into the mechanism of action of ELL family transcription factors, and they bring to light direct ro...

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mentioning

confidence: 90%

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL

Kong

Banks

Shilatifard

et al. 2005

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

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“…Previously, the full-length dELL cDNA had been cloned and inserted into a pRSET vector containing an upstream in-frame N-terminal His-6 epitope tag and an Express epitope tag (16). The epitope-tagged dELL cDNA was excised from this recombinant as an NdeI-EcoRI restriction fragment, and both ends were blunted by the Klenow fragment.…”

Section: Transgene Rescue Construct and Detection Of Transgenic Dell mentioning

confidence: 99%

“…The resulting construct was then used to generate transgenic lines for subsequent rescue experiments and immunocytological analysis. Immunostaining was with 6xHis-Gly Ab (Invitrogen) as described (16).…”

Section: Transgene Rescue Construct and Detection Of Transgenic Dell mentioning

confidence: 99%

“…A 6xHis-tagged dELL cDNA fragment was fused downstream of the promoter and first intron of the ubiquitously expressed Chip gene (21). Previous studies showed that 6xHis-tagged dELL is associated with Pol II in transgenic fly extracts (16). Expression of epitope-tagged dELL from the transgene was verified by immunostaining of transgenic polytene chromosomes (Fig.…”

Section: A Dell Transgene Complements the Recessive Lethality Of Su(tpl)mentioning

confidence: 99%

“…In Drosophila, the unique ELL family gene dELL enhances Pol II elongation in vitro and is associated with Pol II on chromosomes and in fly extract (16). dELL is expressed in all cell types examined, and at all developmental stages, suggesting it could play a widespread role in gene transcription during development.…”

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confidence: 99%

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dELL is an essential RNA polymerase II elongation factor with a general role in development

Eissenberg

Gerber

et al. 2002

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

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Several eukaryotic proteins increase RNA polymerase II (Pol II) transcription rates in vitro. The relative contributions of these factors to gene expression in vivo is unknown. The ELL family of proteins promote Pol II elongation in vitro, and the Drosophila ELL homolog (dELL) is associated with Pol II at sites of transcription in vivo. The purpose of this study was to test whether an ELL family protein is required for gene expression in vivo. We show that dELL is encoded by the Suppressor of Triplo-lethal locus [Su(Tpl)]. We have characterized seven distinct mutant alleles of Su(Tpl) and show that a dELL transgene rescues recessive lethality of Su(Tpl). Su(Tpl) mutations cause abnormal embryonic segmentation and dominantly modify expression of diverse genes during development. These data show that an ELL family elongation factor is essential, acts broadly in development, and is not functionally redundant to other elongation factors in vivo.

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Banding patterns in Drosophila melanogaster polytene chromosomes correlate with DNA‐binding protein occupancy

et al. 2012

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The most enigmatic feature of polytene chromosomes is their banding pattern, the genetic organization of which has been a very attractive puzzle for many years. Recent genome-wide protein mapping efforts have produced a wealth of data for the chromosome proteins of Drosophila cells. Based on their specific protein composition, the chromosomes comprise two types of bands, as well as interbands. These differ in terms of time of replication and specific types of proteins. The interbands are characterized by their association with "active" chromatin proteins, nucleosome remodeling, and origin recognition complexes, and so they have three functions: acting as binding sites for RNA pol II, initiation of replication and nucleosome remodeling of short fragments of DNA. The borders and organization of the same band and interband regions are largely identical, irrespective of the cell type studied. This demonstrates that the banding pattern is a universal principle of the organization of interphase polytene and non-polytene chromosomes.

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Drosophila ELL is associated with actively elongating RNA polymerase II on transcriptionally active sites in vivo

Cited by 58 publications

References 68 publications

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL

dELL is an essential RNA polymerase II elongation factor with a general role in development

Banding patterns in Drosophila melanogaster polytene chromosomes correlate with DNA‐binding protein occupancy

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