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Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages

BACKGROUND: Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; howev...

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Autores principales: Morita, Mariko, Nakamura, Megumi, Hamada, Michito, Takahashi, Satoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287487/
https://www.ncbi.nlm.nih.gov/pubmed/22784578
http://dx.doi.org/10.1186/1752-0509-5-S2-S7
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author Morita, Mariko
Nakamura, Megumi
Hamada, Michito
Takahashi, Satoru
author_facet Morita, Mariko
Nakamura, Megumi
Hamada, Michito
Takahashi, Satoru
author_sort Morita, Mariko
collection PubMed
description BACKGROUND: Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory cis-elements (motifs) offers a robust approach. RESULTS: Here, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5’AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in Mafb deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a C1qa promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the C1qa promoter with the GATA-1 motifs and MafB motifs. CONCLUSIONS: These observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of C1qa. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation.
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spelling pubmed-32874872012-02-28 Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages Morita, Mariko Nakamura, Megumi Hamada, Michito Takahashi, Satoru BMC Syst Biol Proceedings BACKGROUND: Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory cis-elements (motifs) offers a robust approach. RESULTS: Here, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5’AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in Mafb deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a C1qa promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the C1qa promoter with the GATA-1 motifs and MafB motifs. CONCLUSIONS: These observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of C1qa. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation. BioMed Central 2011-12-14 /pmc/articles/PMC3287487/ /pubmed/22784578 http://dx.doi.org/10.1186/1752-0509-5-S2-S7 Text en Copyright ©2011 Morita et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Proceedings
Morita, Mariko
Nakamura, Megumi
Hamada, Michito
Takahashi, Satoru
Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
title Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
title_full Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
title_fullStr Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
title_full_unstemmed Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
title_short Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
title_sort combinatorial motif analysis of regulatory gene expression in mafb deficient macrophages
topic Proceedings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287487/
https://www.ncbi.nlm.nih.gov/pubmed/22784578
http://dx.doi.org/10.1186/1752-0509-5-S2-S7
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