NonO enhances the association of many DNA-binding proteins to their targets

Abstract

NonO is an unusual nucleic acid binding protein not only in that it binds both DNA and RNA but that it does so via functionally separable domains. Here we document that NonO enhances the binding of some (E47, OTF-1 and OTF-2) but not all (PEA3) conventional sequence-specific transcription factors to their recognition sites in artificial substrates as well as in an immunoglobulin VHpromoter. We also show that NonO induces the binding of the Ku complex to DNA ends. Ku has no known DNA sequence specificity. These enhancement of binding effects are NonO concentration dependent. Using the E box activity of E47 as a model, kinetic studies demonstrate that the association rate of the protein-DNA complex increases in the presence of NonO while the dissociation rate remains the same, thereby increasing the sum total of the interaction. Oligo competition experiments indicate that NonO does not contact the target DNA in order to enhance the binding activity of DNA binding proteins. Rather, methylation interference analysis reveals that the induced E47 binding-activity has the same DNA-binding sequence specificity as the normal binding. This result suggests that one of the effects of NonO is to induce a true protein-DNA interaction. In this way, it might be possible for NonO to play a crucial role in gene regulation.

TNF-α Suppresses Prolyl-4-Hydroxylase α1 Expression via the ASK1–JNK–NonO Pathway

“…NonO is a 55-kDa ubiquitously expressed protein originally identified as a non-POU domain-containing octamer-binding protein. 25 NonO is highly homologous to the C terminus of PSD 18 ; NonO can bind via its NTH domain to doublestranded DNA with restricted A/T specificity reminiscent of octamer motifs. 26 In addition to its own DNA-binding abilities, NonO has the ability to induce the binding of several transcription factors to their response elements and bind directly to Spi-1/PU.1 transcription factors.…”

p54nrb/NONO Regulates Cyclic AMP-Dependent Glucocorticoid Production by Modulating Phosphodiesterase mRNA Splicing and Degradation

“…DBHS proteins have been described as multifunctional nuclear proteins, with p54 nrb /NONO being implicated in numerous nuclear processes, including transcription regulation, mRNA splicing, nuclear retention, and subnuclear body formation (4)(5)(6)(7). In addition to binding to DNA elements such as intracisternal A particles (8), p54 nrb /NONO is also known to promote the binding of other transcription factors to their response elements (9). The polypyrimidine tract-binding protein-associated splicing factor (PSF)/p54 nrb /NONO heterodimer regulates the transcriptional activity of several nuclear receptors (NRs), including the thyroid hormone receptor (10) and the androgen receptor (11).…”

The Hrp65 self-interaction is mediated by an evolutionarily conserved domain and is required for nuclear import of Hrp65 isoforms that lack a nuclear localization signal

“…regulation (Basu et al, 1997;Yang et al, 1997;Mathur et al, 2001;Sewer et al, 2002;Emili et al, 2002), splicing (Peng et al, 2002) and nuclear retention of viral RNA (Zhang and Carmichael, 2001). In Drosophila, mutations of the NonA gene cause defects in the central nervous system that affect vision and behavior in the fly (Jones and Rubin, 1990;Rendahl et al, 1992), but the function of NonA at the molecular level is unknown.…”