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CIS REGULATORY MODULE DISCOVERY IN TH1 CELL DEVELOPMENT

Indiana University-Purdue University Indianapolis (IUPUI) / Immune response enables the body to resist foreign invasions. The Inflammatory response is an important aspect in the immune response which is articulated by elements such as cytokines, APC, T-cell and B-cell, effector cell or natural killer. Of these elements, T-cells especially T-helper cells; a sub class of T-cells plays a pivotal role in stimulating the immune response by participating in various biological reactions such as, the transcription regulatory network. Transcriptional regulatory mechanisms are mediated by a set of transcription factors (TFs), that bind to a specific region (motifs or transcription factor binding sites, TFBS), on the target gene(s) controlling the expression of genes that are involved in T-helper cell mediated immune response. Eukaryotic regulatory motifs, referred to as cis regulatory modules (CRMs) or cistrome, co-occur with the regulated gene’s transcription start site (TSS) thus, providing all the essential components for building the transcriptional regulatory networks that depends on the relevant TF-TFBS interactions. Here, we study IL-12 stimulated transcriptional regulators in STAT4 mediated T helper 1 (Th1) cell development by focusing on the identification of TFBS and CRMs using a set of Stat4 ChIP-on-chip target genes. A region containing 2000 bases of Mus musculus sequences with the Stat4 binding site, derived from the ChIP-on-chip data, has been characterized for enrichment of other motifs and, thus CRMs. Our experiments identify some potential motifs, (such as NF-κB and PPARγ/RXR) being enriched in the Stat4 binding sequences compared to neighboring background sequences. Furthermore, these predicted CRMs were observed to be associated with biologically relevant target genes in the ChIP-on-chip data set by meaningful gene ontology annotations. These analyses will enable us to comprehend the complicated transcription regulatory network and at the same time categorically analyze the IL-12 stimulated Stat4 mediated Th1 cell differentiation.

Identiferoai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/2678
Date January 2010
CreatorsGanakammal, Satishkumar Ranganathan
ContributorsPerumal, Narayanan B, Kaplan, Mark H., Vahedi, Golnaz
PublisherProceeding ISB '10 Proceedings of the International Symposium on Biocomputing ACM New York, NY, USA ©2010 table of contents ISBN: 978-1-60558-722-6 doi>10.1145/1722024.1722039
Source SetsIndiana University-Purdue University Indianapolis
Languageen_US
Detected LanguageEnglish
TypeThesis

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