Pathway: NPAS4 regulates expression of target genes
Reactions in pathway: NPAS4 regulates expression of target genes :
NPAS4 regulates expression of target genes
NPAS4 is a basic helix loop helix (bHLH) transcription factor that needs to dimerize with another bHLH protein, either ARNT, ARNT2 or ARNTL, in order to be able to bind to target DNA (Ooe et al. 2004; Ooe et al. 2009; Brigidi et al. 2019).
NPAS4 is implicated as a transcriptional regulator of genes involved in neuronal development such as CDK5 (Yun et al. 2013), CDK5R1 (Yun et al. 2013), RBFOX3 (NeuN) (Yun et al. 2013), BDNF (Pruunsild et al. 2011) and RET (Sribudiani et al. 2011), genes involved in synaptogenesis and synaptic transmission such as NPTX2 (Lin et al. 2008), MDM2 (Yoshihara et al. 2014; Lv et al. 2021), FOS (Ramamoorthi et al. 2011), IQSEC3 (Kim et al. 2021), PLK2 (Weng et al. 2018) and possibly other genes (Lin et al. 2008; Shan et al. 2018), circadian rhythm-related genes such as NAMPT (West et al. 2013), and genes involved in neuroprotection upon injury such as GEM (Takahashi et al. 2021), SYT10 (Woitecki et al. 2016) and possibly other genes (Qiu et al. 2013). In pancreatic beta-cell, NPAS4 is implicated as a regulator of insulin synthesis under stress conditions (Sabatini et al. 2013).
The circadian clock regulated gene CRY1 was identified as NPAS4 target gene in sheep brain (West et al. 2013), but this finding was not reproduced in the high throughput identification of NPAS4 targets in rat primary neurons (Brigidi et al. 2019). The DBNL gene, encoding Drebrin, a dendrytic cytoskeleton modulator, was initially identified as a gene directly upregulated by Npas4 (Ooe et al. 2004), but a high throughput study of NPAS4 targets showed DBNL gene expression to be repressed by NPAS4, although not significantly (Brigidi et al. 2019).
NPAS4 is expressed in endothelial cells and may play a role in angiogenesis (Esser et al. 2017).
NPAS4 is implicated as a transcriptional regulator of genes involved in neuronal development such as CDK5 (Yun et al. 2013), CDK5R1 (Yun et al. 2013), RBFOX3 (NeuN) (Yun et al. 2013), BDNF (Pruunsild et al. 2011) and RET (Sribudiani et al. 2011), genes involved in synaptogenesis and synaptic transmission such as NPTX2 (Lin et al. 2008), MDM2 (Yoshihara et al. 2014; Lv et al. 2021), FOS (Ramamoorthi et al. 2011), IQSEC3 (Kim et al. 2021), PLK2 (Weng et al. 2018) and possibly other genes (Lin et al. 2008; Shan et al. 2018), circadian rhythm-related genes such as NAMPT (West et al. 2013), and genes involved in neuroprotection upon injury such as GEM (Takahashi et al. 2021), SYT10 (Woitecki et al. 2016) and possibly other genes (Qiu et al. 2013). In pancreatic beta-cell, NPAS4 is implicated as a regulator of insulin synthesis under stress conditions (Sabatini et al. 2013).
The circadian clock regulated gene CRY1 was identified as NPAS4 target gene in sheep brain (West et al. 2013), but this finding was not reproduced in the high throughput identification of NPAS4 targets in rat primary neurons (Brigidi et al. 2019). The DBNL gene, encoding Drebrin, a dendrytic cytoskeleton modulator, was initially identified as a gene directly upregulated by Npas4 (Ooe et al. 2004), but a high throughput study of NPAS4 targets showed DBNL gene expression to be repressed by NPAS4, although not significantly (Brigidi et al. 2019).
NPAS4 is expressed in endothelial cells and may play a role in angiogenesis (Esser et al. 2017).
RNA polymerase II (Pol II) is the central enzyme that catalyses DNA- directed mRNA synthesis during the transcription of protein-coding genes. Pol II consists of a 10-subunit catalytic core, which alone is capable of elongating the RNA transcript, and a complex of two subunits, Rpb4/7, that is required for transcription initiation.
The transcription cycle is divided in three major phases: initiation, elongation, and termination. Transcription initiation include promoter DNA binding, DNA melting, and initial synthesis of short RNA transcripts. The transition from initiation to elongation, is referred to as promoter escape and leads to a stable elongation complex that is characterized by an open DNA region or transcription bubble. The bubble contains the DNA-RNA hybrid, a heteroduplex of eight to nine base pairs. The growing 3-end of the RNA is engaged with the polymerase complex active site. Ultimately transcription terminates and Pol II dissocitates from the template.
The transcription cycle is divided in three major phases: initiation, elongation, and termination. Transcription initiation include promoter DNA binding, DNA melting, and initial synthesis of short RNA transcripts. The transition from initiation to elongation, is referred to as promoter escape and leads to a stable elongation complex that is characterized by an open DNA region or transcription bubble. The bubble contains the DNA-RNA hybrid, a heteroduplex of eight to nine base pairs. The growing 3-end of the RNA is engaged with the polymerase complex active site. Ultimately transcription terminates and Pol II dissocitates from the template.
Gene expression encompasses transcription and translation and the regulation of these processes. RNA Polymerase I Transcription produces the large preribosomal RNA transcript (45S pre-rRNA) that is processed to yield 18S rRNA, 28S rRNA, and 5.8S rRNA, accounting for about half the RNA in a cell. RNA Polymerase II transcription produces messenger RNAs (mRNA) as well as a subset of non-coding RNAs including many small nucleolar RNAs (snRNA) and microRNAs (miRNA). RNA Polymerase III Transcription produces transfer RNAs (tRNA), 5S RNA, 7SL RNA, and U6 snRNA. Transcription from mitochondrial promoters is performed by the mitochondrial RNA polymerase, POLRMT, to yield long transcripts from each DNA strand that are processed to yield 12S rRNA, 16S rRNA, tRNAs, and a few RNAs encoding components of the electron transport chain. Regulation of gene expression can be divided into epigenetic regulation, transcriptional regulation, and post-transcription regulation (comprising translational efficiency and RNA stability). Epigenetic regulation of gene expression is the result of heritable chemical modifications to DNA and DNA-binding proteins such as histones. Epigenetic changes result in altered chromatin complexes that influence transcription. Gene Silencing by RNA mostly occurs post-transcriptionally but can also affect transcription. Small RNAs originating from the genome (miRNAs) or from exogenous RNA (siRNAs) are processed and transferred to the RNA-induced silencing complex (RISC), which interacts with complementary RNA to cause cleavage, translational inhibition, or transcriptional inhibition.