Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TFIIE and TFIIH are essential for the promoter opening and escape that occurs as RNA polymerase II transits into early elongation. XPB, a subunit of TFIIH, contains an ATP-dependent helicase activity that is used in both of these processes. Here, we show that the smaller beta subunit of TFIIE stimulates the XPB helicase and ATPase activities. The larger alpha subunit can use its known inhibitory activity to moderate the stimulation by the beta subunit. Regions of TFIIE beta required for the helicase stimulation were identified. Mutants were constructed that are defective in stimulating the XPB helicase but still allow intact TFIIE to bind and recruit XPB and TFIIH to form the pre-initiation complex. In a test for the functional significance of the stimulatory effect of TFIIE beta, these mutant forms of TFIIE were shown to be defective in a transcription assay on linear DNA. The data suggest that the beta subunit of TFIIE is an ATPase and helicase co-factor that can assist the XPB subunit of TFIIH during transcription initiation and the transition to early elongation, enhancing the potential diversity of regulatory targets.
...
PMID:Stimulation of the XPB ATP-dependent helicase by the beta subunit of TFIIE. 1591 39

DNA helicases open the duplex during DNA replication, repair and transcription. However, RNA polymerase II is the only member of its family with this requirement; RNA polymerases I and III and bacterial RNA polymerases open DNA without a helicase. In this report, characterization of XPB mutants indicates that its helicase activity is not used for RNA polymerase II promoter opening, which is instead driven by its ATPase activity. The mutants have parallels in sigma(54) bacterial transcription and this suggests a similar mode of opening DNA for both RNA polymerases, involving ATP-dependent enzyme conformational changes. Promoter escape is defective in these XPB mutants, suggesting that the XPB helicase acts as an ATP-driven motor to reorganize the tightly wrapped multiprotein eukaryotic preinitiation complex during the remodeling that precedes elongation and the coupling to RNA processing events.
...
PMID:TFIIH XPB mutants suggest a unified bacterial-like mechanism for promoter opening but not escape. 1593 91

The Drosophila trithorax group gene brahma (brm) encodes the ATPase subunit of a 2-MDa chromatin-remodeling complex. brm was identified in a screen for transcriptional activators of homeotic genes and subsequently shown to play a global role in transcription by RNA polymerase II. To gain insight into the targeting, function, and regulation of the BRM complex, we screened for mutations that genetically interact with a dominant-negative allele of brm (brm(K804R)). We first screened for dominant mutations that are lethal in combination with a brm(K804R) transgene under control of the brm promoter. In a distinct but related screen, we identified dominant mutations that modify eye defects resulting from expression of brm(K804R) in the eye-antennal imaginal disc. Mutations in three classes of genes were identified in our screens: genes encoding subunits of the BRM complex (brm, moira, and osa), other proteins directly involved in transcription (zerknullt and RpII140), and signaling molecules (Delta and vein). Expression of brm(K804R) in the adult sense organ precursor lineage causes phenotypes similar to those resulting from impaired Delta-Notch signaling. Our results suggest that signaling pathways may regulate the transcription of target genes by regulating the activity of the BRM complex.
...
PMID:Genetic screens for enhancers of brahma reveal functional interactions between the BRM chromatin-remodeling complex and the delta-notch signal transduction pathway in Drosophila. 1594 53

Covalent modifications to histones are key epigenetic marks that control gene transcription. Multiple lysine residues on histone H3 are methylated (me), but their functions are unclear. Here, we demonstrate two phases of combinatorial and dynamic H3 methylation during induction of transcription at MET16 in yeast. K4me3 with K36me2/3 define a postinitiation regulatory phase and precede the appearance of K4me2 with K79me2 at the onset of transcript elongation. The Isw1 ATPase delays the release of initiated RNA polymerase II (RNAPII) into elongation to facilitate chromatin modifications. The Spp1 subunit of complex associated with Set1 (COMPASS) and Set2, determining K4me3 and K36me2/3, respectively, are required for transient NuA4-dependent H4K8ac. This releases RNAPII from Isw1 control and promotes controlled transcription elongation and termination. We propose that newly initiated RNAPII is under epigenetic control.
...
PMID:Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription. 1594 46

This study investigated effects of prolonged submaximal exercise on Na+-K+-ATPase mRNA and protein expression, maximal activity, and content in human skeletal muscle. We also investigated the effects on mRNA expression of the transcription initiator gene, RNA polymerase II (RNAP II), and key genes involved in protein translation, eukaryotic initiation factor-4E (eIF-4E) and 4E-binding protein 1 (4E-BP1). Eleven subjects (6 men, 5 women) cycled at 75.5% (SD 4.8%) peak O2 uptake and continued until fatigue. A vastus lateralis muscle biopsy was taken at rest, fatigue, and 3 and 24 h postexercise. We analyzed muscle for Na+-K+-ATPase alpha1, alpha2, alpha3, beta1, beta2, and beta3, as well for RNAP II, eIF-4E, and 4E-BP1 mRNA expression by real-time RT-PCR and Na+-K+-ATPase isoform protein abundance using immunoblotting. Muscle homogenate maximal Na+-K+-ATPase activity was determined by 3-O-methylfluorescein phosphatase activity and Na+-K+-ATPase content by [3H]ouabain binding. Cycling to fatigue [54.5 (SD 20.6) min] immediately increased alpha3 (P = 0.044) and beta2 mRNA (P = 0.042) by 2.2- and 1.9-fold, respectively, whereas alpha1 mRNA was elevated by 2.0-fold at 24 h postexercise (P = 0.036). A significant time main effect was found for alpha3 protein abundance (P = 0.046). Exercise transiently depressed maximal Na+-K+-ATPase activity (P = 0.004), but Na+-K+-ATPase content was unaltered throughout recovery. Exercise immediately increased RNAP II mRNA by 2.6-fold (P = 0.011) but had no effect on eIF-4E and 4E-BP1 mRNA. Thus a single bout of prolonged submaximal exercise induced isoform-specific Na+-K+-ATPase responses, increasing alpha1, alpha3, and beta2 mRNA but only alpha3 protein expression. Exercise also increased mRNA expression of RNAP II, a gene initiating transcription, but not of eIF-4E and 4E-BP1, key genes initiating protein translation.
...
PMID:Prolonged submaximal exercise induces isoform-specific Na+-K+-ATPase mRNA and protein responses in human skeletal muscle. 1617 92

Loss of a nonenzymatic function of XPG results in defective transcription-coupled repair (TCR), Cockayne syndrome (CS), and early death, but the molecular basis for these phenotypes is unknown. Mutation of CSB, CSA, or the TFIIH helicases XPB and XPD can also cause defective TCR and CS. We show that XPG interacts with elongating RNA polymerase II (RNAPII) in the cell and binds stalled RNAPII ternary complexes in vitro both independently and cooperatively with CSB. XPG binds transcription-sized DNA bubbles through two domains not required for incision and functionally interacts with CSB on these bubbles to stimulate its ATPase activity. Bound RNAPII blocks bubble incision by XPG, but an ATP hydrolysis-dependent process involving TFIIH creates access to the junction, allowing incision. Together, these results implicate coordinated recognition of stalled transcription by XPG and CSB in TCR initiation and suggest that TFIIH-dependent remodeling of stalled RNAPII without release may be sufficient to allow repair.
...
PMID:Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome. 1624 22

Thyroid hormone receptors (TRs) are ligand-regulated transcription factors that bind to thyroid hormone response elements of target genes. Upon ligand binding, they recruit coactivator complexes that increase histone acetylation and recruit RNA polymerase II (Pol II) to activate transcription. Recent studies suggest that nuclear receptors and coactivators may have temporal recruitment patterns on hormone response elements, yet little is known about the nature of the patterns at multiple endogenous target genes. We thus performed chromatin immunoprecipitation assays to investigate coactivator recruitment and histone acetylation patterns on the thyroid hormone response elements of four endogenous target genes (GH, sarcoplasmic endoplasmic reticulum calcium-adenosine triphosphatase, phosphoenolpyruvate carboxykinase, and cholesterol 7alpha-hydroxylase) in a rat pituitary cell line that expresses TRs. We found that TRbeta, several associated coactivators (steroid receptor coactivator-1, glucocorticoid receptor interacting protein-1, and TR-associated protein 220), and RNA Pol II were rapidly recruited to thyroid hormone response elements as early as 15 min after T3 addition. When the four target genes were compared, we observed differences in the types and temporal patterns of recruited coactivators and histone acetylation. Interestingly, the temporal pattern of RNA Pol II was similar for three genes studied. Our findings suggest that thyroid hormone-regulated target genes may have distinct patterns of coactivator recruitment and histone acetylation that may enable highly specific regulation.
...
PMID:Thyroid hormone-regulated target genes have distinct patterns of coactivator recruitment and histone acetylation. 1625 15

Promoter recruitment of the Saccharomyces cerevisiae SAGA histone acetyltransferase complex is required for RNA polymerase II-dependent transcription of several genes. SAGA is targeted to promoters through interactions with sequence-specific DNA binding transcriptional activators and facilitates preinitiation-complex assembly and transcription. Here, we show that the 19S proteasome regulatory particle (19S RP) alters SAGA to stimulate its interaction with transcriptional activators. The ATPase components of the 19S RP are required for stimulation of SAGA/activator interactions and enhance SAGA recruitment to promoters. Proteasomal ATPases genetically interact with SAGA, and their inhibition reduces global histone H3 acetylation levels and SAGA recruitment to target promoters in vivo. These results indicate that the 19S RP modulates SAGA complex using its ATPase components, thereby facilitating subsequent transcription events at promoters.
...
PMID:The proteasome regulatory particle alters the SAGA coactivator to enhance its interactions with transcriptional activators. 1626 25

Cyclin-dependent kinase 9 (Cdk9) of fission yeast is an essential ortholog of metazoan positive transcription elongation factor b (P-TEFb), which is proposed to coordinate capping and elongation of RNA polymerase II (Pol II) transcripts. Here we show that Cdk9 is activated to phosphorylate Pol II and the elongation factor Spt5 by Csk1, one of two fission yeast CDK-activating kinases (CAKs). Activation depends on Cdk9 T-loop residue Thr-212. The other CAK-Mcs6, the kinase component of transcription factor IIH (TFIIH)-cannot activate Cdk9. Consistent with the specificities of the two CAKs in vitro, the kinase activity of Cdk9 is reduced approximately 10-fold by csk1 deletion, and Cdk9 complexes from csk1Delta but not csk1+ cells can be activated by Csk1 in vitro. A cdk9(T212A) mutant is viable but phenocopies conditional growth defects of csk1Delta strains, indicating a role for Csk1-dependent activation of Cdk9 in vivo. A cdk9(T212A) mcs6(S165A) strain, in which neither Cdk9 nor Mcs6 can be activated by CAK, has a synthetic growth defect, implying functional overlap between the two CDKs, which have distinct but overlapping substrate specificities. Cdk9 forms complexes in vivo with the essential cyclin Pch1 and with Pcm1, the mRNA cap methyltransferase. The carboxyl-terminal region of Cdk9, through which it interacts with another capping enzyme, the RNA triphosphatase Pct1, is essential. Together, the data support a proposed model whereby Cdk9/Pch1-the third essential CDK-cyclin complex described in fission yeast-helps to target the capping apparatus to the transcriptional elongation complex.
...
PMID:Cyclin-dependent kinase 9 (Cdk9) of fission yeast is activated by the CDK-activating kinase Csk1, overlaps functionally with the TFIIH-associated kinase Mcs6, and associates with the mRNA cap methyltransferase Pcm1 in vivo. 1642 35

Tissue-specific activation of the osteocalcin (OC) gene is associated with changes in chromatin structure at the promoter region. Two nuclease-hypersensitive sites span the key regulatory elements that control basal tissue-specific and vitamin D3-enhanced OC gene transcription. To gain understanding of the molecular mechanisms involved in chromatin remodeling of the OC gene, we have examined the requirement for SWI/SNF activity. We inducibly expressed an ATPase-defective BRG1 catalytic subunit that forms inactive SWI/SNF complexes that bind to the OC promoter. This interaction results in inhibition of both basal and vitamin D3-enhanced OC gene transcription and a marked decrease in nuclease hypersensitivity. We find that SWI/SNF is recruited to the OC promoter via the transcription factor CCAAT/enhancer-binding protein beta, which together with Runx2 forms a stable complex to facilitate RNA polymerase II binding and activation of OC gene transcription. Together, our results indicate that the SWI/SNF complex is a key regulator of the chromatin-remodeling events that promote tissue-specific transcription in osteoblasts.
...
PMID:Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity. 1677 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---