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Transcriptional Network (transcriptional + network)
Selected AbstractsAn endoderm-specific transcriptional enhancer from the mouse Gata4 gene requires GATA and homeodomain protein,binding sites for function in vivoDEVELOPMENTAL DYNAMICS, Issue 10 2009Anabel Rojas Abstract Several transcription factors function in the specification and differentiation of the endoderm, including the zinc finger transcription factor GATA4. Despite its essential role in endoderm development, the transcriptional control of the Gata4 gene in the developing endoderm and its derivatives remains incompletely understood. Here, we identify a distal enhancer from the Gata4 gene, which directs expression exclusively to the visceral and definitive endoderm of transgenic mouse embryos. The activity of this enhancer is initially broad within the definitive endoderm but later restricts to developing endoderm-derived tissues, including pancreas, glandular stomach, and duodenum. The activity of this enhancer in vivo is dependent on evolutionarily-conserved HOX- and GATA-binding sites, which are bound by PDX-1 and GATA4, respectively. These studies establish Gata4 as a direct transcriptional target of homeodomain and GATA transcription factors in the endoderm and support a model in which GATA4 functions in the transcriptional network for pancreas formation. Developmental Dynamics 238:2588,2598, 2009. © 2009 Wiley-Liss, Inc. [source] The basic helix-loop-helix factor Hand2 regulates autonomic nervous system developmentDEVELOPMENTAL DYNAMICS, Issue 3 2005Yuka Morikawa Abstract Mammalian autonomic nervous system (ANS) development requires the combinatorial action of a number of transcription factors, which include Mash1, Phox2b, and GATA3. Here we show that the bHLH transcription factor, Hand2 (dHAND), is expressed concurrently with Mash1 during sympathetic nervous system (SNS) development and that the expression of Hand2 is not dependent on Mash1. This suggests that these two bHLH factors work in parallel during SNS development. We also show that ectopic expression of Hand2 activates the neuronal program and promotes the acquisition of a phenotype corresponding to peripheral neurons including neurons of the SNS lineage in P19 embryonic carcinoma cells. We propose that Hand2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mash1. We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand2 functions to promote ANS development as part of a larger transcriptional complex. Developmental Dynamics 234:613,621, 2005. © 2005 Wiley-Liss, Inc. [source] Sp1 and krüppel-like factor family of transcription factors in cell growth regulation and cancerJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2001Adrian R. Black The Sp/KLF family contains at least twenty identified members which include Sp1-4 and numerous krüppel-like factors. Members of the family bind with varying affinities to sequences designated as ,Sp1 sites' (e.g., GC-boxes, CACCC-boxes, and basic transcription elements). Family members have different transcriptional properties and can modulate each other's activity by a variety of mechanisms. Since cells can express multiple family members, Sp/KLF factors are likely to make up a transcriptional network through which gene expression can be fine-tuned. ,Sp1 site'-dependent transcription can be growth-regulated, and the activity, expression, and/or post-translational modification of multiple family members is altered with cell growth. Furthermore, Sp/KLF factors are involved in many growth-related signal transduction pathways and their overexpression can have positive or negative effects on proliferation. In addition to growth control, Sp/KLF factors have been implicated in apoptosis and angiogenesis; thus, the family is involved in several aspects of tumorigenesis. Consistent with a role in cancer, Sp/KLF factors interact with oncogenes and tumor suppressors, they can be oncogenic themselves, and altered expression of family members has been detected in tumors. Effects of changes in Sp/KLF factors are context-dependent and can appear contradictory. Since these factors act within a network, this diversity of effects may arise from differences in the expression profile of family members in various cells. Thus, it is likely that the properties of the overall network of Sp/KLF factors play a determining role in regulation of cell growth and tumor progression. © 2001 Wiley-Liss, Inc. [source] Regulation of retinal ganglion cell gene expression by bHLH transcription factors in the developing and ischemic retinasACTA OPHTHALMOLOGICA, Issue 2009JM MATTER Purpose The loss of retinal ganglion cells (RGC) in the glaucomatous retina exhibits similarities to the pattern of neuronal degeneration detected after experimental ischemia. However, a short episode of retinal ischemia does not provoke damage but rather triggers an endogenous form of neuroprotection. HIFs are bHLH proteins that regulate hypoxic response in ischemic retinas and they are involved in neuroprotection. Hypoxic environments also occur in the developing embryo and create specific niches controlling cell differentiation. Genetic analyses of HIF functions have revealed the importance of oxygen as a key regulator of ontogeny. We have compared the transcriptomes of RGCs in ischemic versus developing retinas. Methods Genome-wide screens were conducted to identify genes which are expressed in newborn RGCs and growing optic nerve axons and which are up- or down-regulated after venal occlusion by photodynamic thrombosis in the rat retinas. Results Atoh7 is a bHLH protein which is central to the transcriptional network regulating the production of RGCs. Among the targets of Atoh7 there are genes involved in the general metabolism and energy supply , e.g., alpha-enolase (ENO1), glucose-6 -phosphate isomerase (GPI). These glycolytic enzymes are also targets of HIFs and they are upregulated during hypoxia. To investigate the linkage of glycolysis and mitochondrial activity in RGCs, we monitored by confocal time-lapse imaging the dynamic distribution of mitochondria in the cell bodies and axons of RGCs that express HIF/Atoh7 targets in developing and ischemic retinas. Conclusion Some gene expression programs involved in differentiating RGCs might be reinitiated in neuroprotection. [source] Type III effectors orchestrate a complex interplay between transcriptional networks to modify basal defence responses during pathogenesis and resistanceTHE PLANT JOURNAL, Issue 1 2006William Truman Summary To successfully infect a plant, bacterial pathogens inject a collection of Type III effector proteins (TTEs) directly into the plant cell that function to overcome basal defences and redirect host metabolism for nutrition and growth. We examined (i) the transcriptional dynamics of basal defence responses between Arabidopsis thaliana and Pseudomonas syringae and (ii) how basal defence is subsequently modulated by virulence factors during compatible interactions. A set of 96 genes displaying an early, sustained induction during basal defence was identified. These were also universally co-regulated following other bacterial basal resistance and non-host responses or following elicitor challenges. Eight hundred and eighty genes were conservatively identified as being modulated by TTEs within 12 h post-inoculation (hpi), 20% of which represented transcripts previously induced by the bacteria at 2 hpi. Significant over-representation of co-regulated transcripts encoding leucine rich repeat receptor proteins and protein phosphatases were, respectively, suppressed and induced 12 hpi. These data support a model in which the pathogen avoids detection through diminution of extracellular receptors and attenuation of kinase signalling pathways. Transcripts associated with several metabolic pathways, particularly plastid based primary carbon metabolism, pigment biosynthesis and aromatic amino acid metabolism, were significantly modified by the bacterial challenge at 12 hpi. Superimposed upon this basal response, virulence factors (most likely TTEs) targeted genes involved in phenylpropanoid biosynthesis, consistent with the abrogation of lignin deposition and other wall modifications likely to restrict the passage of nutrients and water to the invading bacteria. In contrast, some pathways associated with stress tolerance are transcriptionally induced at 12 hpi by TTEs. [source] |