Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The upstream binding factor, UBF, is an RNA polymerase I transcription factor which contains multiple DNA binding domains and a novel protein dimerization domain. Active UBF forms homodimers in vivo through the intramolecular interactions of its dimerization domain, which spans a hundred amino-terminal residues. In the presence of both UBF dimerization domain and its immediately adjacent lysine-rich basic DNA binding domain, the E. coli expressed recombinant polypeptide, dbUBF (dimerization plus basic motifs of UBF), forms homodimers in vitro and binds to double-stranded DNA nonselectively. In gel retardation assay, dbUBF dimers make multiple shift-ladders corresponding to numerous protein dimer-DNA complexes. The UBF dimerization domain contains multiple helical structures, as predicted by EMBO-PHD program. Most of hydrophobic residues in the dimerization domain are confined in the hydrophobic phase of these hypothetic helices. Mutating these hydrophobic residues to glutamate prohibits dbUBF association and gives a different shift pattern in gel retardation assay. The results we present here argue that UBF association is largely exerted by the hydrophobic interactions between the multiple helices to bring two molecules together.
 ...
PMID:The dimerization domain upstream binding factor contains multiple helical structures. 860 48

Hepatitis B virus (HBV) gene expression is mainly regulated at the transcription initiation level. The viral X protein (pX) is a transcription coactivator/mediator targeting TFIIB for the recruitment of RNA polymerase II. Here we report a novel pX nuclear target designated HBXAP (hepatitis B virus X-associated protein). HBXAP is a novel cellular nuclear protein containing a PHD (plant homology domain) finger, a domain shared by many proteins that play roles in chromatin remodeling, transcription coactivation, and oncogenesis. pX physically interacts with HBXAP in vitro and in vivo via the HBXAP region containing the PHD finger. At the functional level HBXAP increases HBV transcription in a pX-dependent manner suggesting a role for this interaction in the virus life cycle. Interestingly, HBXAP collaborates with pX in coactivating the transcriptional activator NF-kappaB. Coactivation of NF-kappaB was also observed in tumor necrosis factor alpha-treated cells suggesting that pX-HBXAP functional collaboration localized downstream to the NF-kappaB nuclear import. Collectively our data suggest that pX recruits and potentiates a novel putative transcription coactivator to regulate NF-kappaB. The implication of pX-HBXAP interaction in the development of hepatocellular carcinoma is discussed.
 ...
PMID:Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription. 1178 98

The new transcriptional coactivator SAYP binds at many sites to transcriptionally active chromatin of polytene chromosomes, colocalizes with RNA polymerase II, and coactivates transcription. On the other hand, SAYP is present in heterochromatic regions of chromosome IV and in the chromocenter and suppresses transcription of transgenes located in heterochromatin. The conserved SAY domain of SAYP is involved in transcription activation, while its PHD domains are responsible for gene silencing in heterochromatin. Thus, SAYP plays a dual role in regulating transcription in euchromatic and heterochromatic regions.
 ...
PMID:[Transcriptional coactivator SAYP can suppress transcription in heterochromatin]. 1616 22

Ubiquitin, and components of the ubiquitin-proteasome system, feature extensively in the regulation of gene transcription. Although there are many examples of how ubiquitin controls the activity of transcriptional regulators and coregulators, there are few examples of core components of the transcriptional machinery that are directly controlled by ubiquitin-dependent processes. The budding yeast protein Asr1 is the prototypical member of the RPC (RING, PHD, CBD) family of ubiquitin-ligases, characterized by the presence of amino-terminal RING (really interesting new gene) and PHD (plant homeo domain) fingers and a carboxyl-terminal domain that directly binds the largest subunit of RNA polymerase II (pol II), Rpb1, in response to phosphorylation events tied to the initiation of transcription. Asr1-mediated oligo-ubiquitylation of pol II leads to ejection of two core subunits of the enzyme and is associated with inhibition of polymerase function. Here, we present evidence that Asr1-mediated ubiquitylation of pol II is required for silencing of subtelomeric gene transcription. We show that Asr1 associates with telomere-proximal chromatin and that disruption of the ubiquitin-ligase activity of Asr1--or mutation of ubiquitylation sites within Rpb1--induces transcription of silenced gene sequences. In addition, we report that Asr1 associates with the Ubp3 deubiquitylase and that Asr1 and Ubp3 play antagonistic roles in setting transcription levels from silenced genes. We suggest that control of pol II by nonproteolytic ubiquitylation provides a mechanism to enforce silencing by transient and reversible inhibition of pol II activity at subtelomeric chromatin.
 ...
PMID:Antagonistic roles for the ubiquitin ligase Asr1 and the ubiquitin-specific protease Ubp3 in subtelomeric gene silencing. 2678 77

A large proportion of fungal genomes are under the control of light. Most fungi employ complex light sensing systems, consisting of red-, blue-, and in some cases green-light photoreceptors. Here we studied the light response in Aspergillus nidulans. In a genetic screen, followed by whole-genome sequencing we identified a global regulator, which appears to be involved in chromatin structure modification. We therefore named the protein RlcA (regulator of light sensing and chromatin remodeling). The protein comprises a nuclear localization signal, a PHD (plant homeodomain) finger, a TFSII (found in the central region of the transcription elongation factor S-II), and a SPOC domain (Spen paralog and ortholog C-terminal domain). In the mutant, where light-controlled genes were constitutively active, the SPOC domain is missing. RlcA localized to the nucleus and interacted with the phytochrome FphA. The PHD-finger domain probably binds to trimethylated lysine 4 of histone H3, whereas the TFSII domain binds RNA polymerase II. The SPOC domain could mediate interaction with a global repressor protein. In the mutant, repressor recruitment would be hindered, whereas in the wild type repressor release would be induced after light stimulation. Our results add another layer of complexity to light sensing in filamentous fungi.
 ...
PMID:On the role of the global regulator RlcA in red-light sensing in Aspergillus nidulans. 3238 7