40
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Comparative analysis of cis-regulation following stroke and seizures in subspaces of conserved eigensystems

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          It is often desirable to separate effects of different regulators on gene expression, or to identify effects of the same regulator across several systems. Here, we focus on the rat brain following stroke or seizures, and demonstrate how the two tasks can be approached simultaneously.

          Results

          We applied SVD to time-series gene expression datasets from the rat experimental models of stroke and seizures. We demonstrate conservation of two eigensystems, reflecting inflammation and/or apoptosis (eigensystem 2) and neuronal synaptic activity (eigensystem 3), between the stroke and seizures. We analyzed cis-regulation of gene expression in the subspaces of the conserved eigensystems. Bayesian networks analysis was performed separately for either experimental model, with cross-system validation of the highest-ranking features. In this way, we correctly re-discovered the role of AP1 in the regulation of apoptosis, and the involvement of Creb and Egr in the regulation of synaptic activity-related genes.

          We identified a novel antagonistic effect of the motif recognized by the nuclear matrix attachment region-binding protein Satb1 on AP1-driven transcriptional activation, suggesting a link between chromatin loop structure and gene activation by AP1. The effects of motifs binding Satb1 and Creb on gene expression in brain conform to the assumption of the linear response model of gene regulation. Our data also suggest that numerous enhancers of neuronal-specific genes are important for their responsiveness to the synaptic activity.

          Conclusion

          Eigensystems conserved between stroke and seizures separate effects of inflammation/apoptosis and neuronal synaptic activity, exerted by different transcription factors, on gene expression in rat brain.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          JNK signaling in apoptosis.

          Jun N-terminal kinases or JNKs play a critical role in death receptor-initiated extrinsic as well as mitochondrial intrinsic apoptotic pathways. JNKs activate apoptotic signaling by the upregulation of pro-apoptotic genes through the transactivation of specific transcription factors or by directly modulating the activities of mitochondrial pro- and antiapoptotic proteins through distinct phosphorylation events. This review analyses our present understanding of the role of JNK in apoptotic signaling and the various mechanisms by which JNK promotes apoptosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Function and regulation of CREB family transcription factors in the nervous system.

            CREB and its close relatives are now widely accepted as prototypical stimulus-inducible transcription factors. In many cell types, these factors function as effector molecules that bring about cellular changes in response to discrete sets of instructions. In neurons, a wide range of extracellular stimuli are capable of activating CREB family members, and CREB-dependent gene expression has been implicated in complex and diverse processes ranging from development to plasticity to disease. In this review, we focus on the current level of understanding of where, when, and how CREB family members function in the nervous system.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Functional organization of the transcriptome in human brain.

              The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain's transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type-specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome.
                Bookmark

                Author and article information

                Journal
                BMC Syst Biol
                BMC Systems Biology
                BioMed Central
                1752-0509
                2010
                17 June 2010
                : 4
                : 86
                Affiliations
                [1 ]Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland
                [2 ]Institute of Informatics, Faculty of Mathematics, Informatics, and Mechanics, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland
                Article
                1752-0509-4-86
                10.1186/1752-0509-4-86
                2902439
                20565733
                fda8524a-861e-4951-b6ac-a494eabae444
                Copyright ©2010 Dabrowski et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 December 2009
                : 17 June 2010
                Categories
                Research article

                Quantitative & Systems biology
                Quantitative & Systems biology

                Comments

                Comment on this article