Nuclear Receptor-Enhanced Transcription Requires Motor- and LSD1-Dependent Gene Networking in Interchromatin Granules

Núñez, Esperanza; Kwon, Young‐Soo; Hutt, Kasey R.; Hu, Qidong; Cardamone, Maria Dafne; Ohgi, Kenneth A.; García-Bassets, Ivan; Rose, David W.; Glass, Christopher K.; Rosenfeld, Michael G.; Fu, Xiang‐Dong

doi:10.1016/j.cell.2008.06.045

Cited by 35 publications

(43 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result demonstrated that although cotranscriptional splicing was poorly efficient in the case of PS2 (leading to the release of unspliced PS2 RNAs from Pol II), a small fraction of nascent PS2 RNAs could be spliced when they were still associated with Pol II. The splicing of at least a small proportion of PS2 RNAs in the vicinity of the PS2 gene was in agreement with a recent report indicating an increase in spliced products close to the PS2 gene in response to E2 (38).…”

Section: Resultssupporting

confidence: 79%

See 1 more Smart Citation

Cotranscriptional Splicing Potentiates the mRNA Production from a Subset of Estradiol-Stimulated Genes

Bittencourt

Dutertre

Sanchez

et al. 2008

Molecular and Cellular Biology

View full text Add to dashboard Cite

While early steps of gene expression, such as transcription preinitiation, are known to often be rate limiting and to be regulated by such stimuli as steroid hormones, the potential impact of downstream steps, including splicing, on the mRNA production rate is unknown. In this work, we studied the effects of the transcriptional stimulus estradiol on cyclin D1, PS2, and c-fos gene expression by measuring the levels of RNA polymerase II on the DNA templates, the levels of nascent transcripts associated with RNA polymerase II, and the levels of unspliced, partially spliced, and fully spliced RNAs. We demonstrated that the efficiency of cotranscriptional splicing of the first intron was higher in the case of cyclin D1 than with PS2 and potentiated the cyclin D1 mRNA production rate. The mechanism involved in cotranscriptional splicing depended on the level of serine 5 phosphorylation of RNA polymerase II at the gene 5 end and on the recruitment of CBP80, one of the two subunits of the cap binding complex, which stimulates splicing of the promoter-proximal intron. Our data indicate that mRNA production from a subset of estradiol-stimulated genes, such as cyclin D1, could occur in a very efficient "assembly line." In contrast, we demonstrated for the first time that despite a strong transcriptional activation of the PS2 gene, the production of mRNA is not optimized owing to inefficient cotranscriptional RNA processing.Gene expression plays a key role in stimulus-dependent regulation of cellular metabolism and fate. Gene expression is a multistep process starting in the nucleus with the synthesis of premessenger RNAs (pre-mRNAs) and with RNA processing (including 5Ј-and 3Ј-end processing and splicing). The mature mRNAs are then exported to the cytosol, where they are translated. Many stimuli, such as steroid hormones, affect the cellular levels of various mRNAs by essentially modulating the transcriptional activities of their target genes. Indeed, steroid hormones (e.g., estrogens) bind to intracellular receptors, which act as ligand-dependent transcription factors and belong to the nuclear receptor superfamily (for reviews, see references 19 and 34). When activated by ligands, nuclear receptors bind to their target gene promoters and serve as platforms for the subsequent recruitment of transcriptional coregulators (for a recent review, see reference 33). With few exceptions (1,26,49), most of the efforts to understand the effects of steroid hormones on mRNA production by their target genes have been made by studying their impact on early steps of the transcriptional process. In this context, a large set of transcriptional coregulators has been shown to play a key role in transcription preinitiation by modulating the chromatin structure of the DNA templates and by recruiting RNA polymerase II (Pol II) (33).However, the transitions between preinitiation, initiation, and transcription elongation can also be rate-limiting steps in various models (8,43,44). These transitions involve specific phosphorylations of the carboxy...

show abstract

Section: Resultssupporting

confidence: 79%

“…6F). This result is in agreement with a recent report showing that spliced PS2 RNAs can be detected at the gene site (38) and suggested that a large proportion of unspliced PS2 RNAs could be released from Pol II (Fig. 3C, 4B, and 6F).…”

Section: Discussionsupporting

confidence: 83%

Cotranscriptional Splicing Potentiates the mRNA Production from a Subset of Estradiol-Stimulated Genes

Bittencourt

Dutertre

Sanchez

et al. 2008

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Factors thought to be involved in this directed activity include TF protein expression levels and TF cooperativity (Das et al 2004), chromatin accessibility or histone modification signatures (Orphanides and Reinberg 2002;Guccione et al 2006), nuclear localization (Nunez et al 2008), and the local sequence environment of the genomic DNA itself (The ENCODE Project Consortium 2007). Gel-shift and similar assays have been the conventional methods of empirically testing transcription factor-DNA interactions.…”

mentioning

confidence: 99%

Functional diversity for REST (NRSF) is defined by in vivo binding affinity hierarchies at the DNA sequence level

Bruce¹,

López-Contreras²,

Flicek³

et al. 2009

Genome Res.

View full text Add to dashboard Cite

The molecular events that contribute to, and result from, the in vivo binding of transcription factors to their cognate DNA sequence motifs in mammalian genomes are poorly understood. We demonstrate that variations within the DNA sequence motifs that bind the transcriptional repressor REST (NRSF) encode in vivo DNA binding affinity hierarchies that contribute to regulatory function during lineage-specific and developmental programs in fundamental ways. First, canonical sequence motifs for REST facilitate strong REST binding and control functional classes of REST targets that are common to all cell types, whilst atypical motifs participate in weak interactions and control those targets, which are cellor tissue-specific. Second, variations in REST binding relate directly to variations in expression and chromatin configurations of REST's target genes. Third, REST clearance from its binding sites is also associated with variations in the RE1 motif. Finally, and most surprisingly, weak REST binding sites reside in DNA sequences that show the highest levels of constraint through evolution, thus facilitating their roles in maintaining tissue-specific functions. These relationships have never been reported in mammalian systems for any transcription factor.

show abstract

“…Several amino acid changes combined with the positional transport process and is dependent on polymeric nuclear actin. 14,18,19 In short, some polymeric forms of actin seem to play important roles in nuclear processes and there is presumably a need for regulation of nuclear actin polymerization.…”

Section: Actin-related Proteins In Actin Dynamicsmentioning

confidence: 99%

Nuclear actin-related proteins take shape

Fenn¹,

Gerhold²,

Hopfner³

2011

BioArchitecture

View full text Add to dashboard Cite

T he function of nuclear actin is poorly understood. It is known to be a discrete component of several chromatin-modifying complexes. Nevertheless, filamentous forms of actin are important for various nuclear processes as well. Nuclear actin is often associated with nuclear actin-related protein Arp4 and other actin-related proteins like Arp8 in the INO80 chromatin remodeler. We recently determined the crystal structure of S. cerevisiae Arp4 that explains why Arp4 is unable to form actin like filaments and shows that it is constitutively bound to an ATP nucleotide. More interestingly, in vitro activities of Arp4 and Arp8 seem to be directed towards stabilizing monomeric actin and to integrate it stoichiometrically into the INO80 complex. Based on this activity, we discuss possible roles of nuclear Arps in chromatin modifying complexes and in regulating more general aspects of nuclear actin dynamics.

show abstract

Nuclear Receptor-Enhanced Transcription Requires Motor- and LSD1-Dependent Gene Networking in Interchromatin Granules

Cited by 35 publications

References 0 publications

Cotranscriptional Splicing Potentiates the mRNA Production from a Subset of Estradiol-Stimulated Genes

Cotranscriptional Splicing Potentiates the mRNA Production from a Subset of Estradiol-Stimulated Genes

Functional diversity for REST (NRSF) is defined by in vivo binding affinity hierarchies at the DNA sequence level

Nuclear actin-related proteins take shape

Contact Info

Product

Resources

About