Genome reading by the NF-κB transcription factors

Abstract

The NF-κB family of dimeric transcription factors regulates transcription by selectively binding to DNA response elements present within promoters or enhancers of target genes. The DNA response elements, collectively known as κB sites or κB DNA, share the consensus 5′-GGGRNNNYCC-3′ (where R, Y and N are purine, pyrimidine and any nucleotide base, respectively). In addition, several DNA sequences that deviate significantly from the consensus have been shown to accommodate binding by NF-κB dimers. X-ray crystal structures of NF-κB in complex with diverse κB DNA have helped elucidate the chemical principles that underlie target selection in vitro. However, NF-κB dimers encounter additional impediments to selective DNA binding in vivo. Work carried out during the past decades has identified some of the barriers to sequence selective DNA target binding within the context of chromatin and suggests possible mechanisms by which NF-κB might overcome these obstacles. In this review, we first highlight structural features of NF-κB:DNA complexes and how distinctive features of NF-κB proteins and DNA sequences contribute to specific complex formation. We then discuss how native NF-κB dimers identify DNA binding targets in the nucleus with support from additional factors and how post-translational modifications enable NF-κB to selectively bind κB sites in vivo.

A novel long non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia.

“…Interestingly, the expression of several of these lncRNAs, such as lincRNA-Cox2 is regulated by the proin ammatory transcription factor NF-κB (31,38,65). NF-κB-mediated transcription of lincRNAs likely coincides with the new protein synthesis driven by early response genes (66) and may allow for lincRNA and protein interactions necessary for secondary and late gene transcription. Similar to lincRNA-Cox2, one of the major ndings of this study is that LPS-induced upregulation of Nostrill appears to be dependent upon NF-κB signaling since two inhibitors of the NF-κB signaling pathway (SC-514, an IKK-2 inhibitor, and JSH-23, an NF-κB p65 inhibitor) signi cantly attenuated Nostrill expression in LPSstimulated BV2 cells (Fig.…”

Effect of statin on semen quality characteristics

“…In addition, stains have been found to ameliorate semen quality characteristics in reproductive toxicity conditions in in vivo systems via other mechanistic routes; for example, a study on obese male rats suggested that fluvastatin protects reproductive function, and hence semen quality, mostly by enhancing signalling of mTOR, which is a human kinase (serine/threonine kinase) involved in several cellular processes such as cell proliferation, cell growth, cell survival and cell motility (Cui, Long, Zhu, & Tian, 2017; Saxton & Sabatini, 2017). Also, oral administration of rosuvastatin at 5 or 10 mg/kg, for 8 weeks, was found to reduce inflammation and cell necrosis may be by decreasing the expression of nuclear factor kappa light‐chain‐enhancer of activated B cells (Mulero, Wang, Huxford, & Ghosh, 2019), a protein that controls DNA transcription and cell survival, caspase‐3, a protein has a vital role in cell apoptosis (Rogers et al, 2017; Wang et al, 2017; Zhu et al, 2018), and inducible nitric oxide synthase, which is an isoform of nitric oxide synthases catalysing the synthesis of nitric oxide from L‐arginine (Banihani, Abu‐Alhayjaa, Amarin, & Alzoubi, 2018; Nathan, 2011), in diabetic rats (Heeba & Hamza, 2015). Furthermore, administration of rosuvastatin restored the degenerative effects in seminiferous tubules as well as weights of epididymis and testes in diabetic rats (Heeba & Hamza, 2015).…”

Learning immune cell differentiation

“…S4c). These nuances may correspond in part to technical noise from model over-parametrization 16 , but they are also expected from known degeneracy in TF binding specificity, which is further influenced by interactions within dimers, as exemplified by the NF-kb family 20 . AI-TAC filters indeed distinguished the canonical NF-kb hetero-dimer (filter231) and homodimer (filter247) motifs.…”

“…S5). Some of the unannotated filters may represent "half-sites", perhaps mere building blocks used by the CNN 43 or perhaps biologically relevant half-sites as reported for NF-kb or NRSF 20,44 .…”

“…Similarly, some TFs are "opportunistic", only binding to chromatin already made accessible by other factors; FoxP3 is in this category 48 , and it is interesting that no TF of the Forkhead family was discovered by AI-TAC, suggesting that Forkhead family factors may not be pioneers in hematopoietic lineages cells as they are in mesenchymal cells 49 . TFs whose binding specificity is very dependent on dimer formation or on cofactors might be difficult for AI-TAC to recognize, although it is interesting to note that it is able to ferret out motifs for NF-kb, a TF family notorious for its combinatorial specificity and tolerance to variation 20 . Relatedly, two factors competing for the same motifs may be poorly resolved by AI-TAC (e.g.…”