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A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia
Microglia are resident mononuclear phagocytes that play a principal role in the maintenance of normal tissue homeostasis in the central nervous system (CNS). Microglia, rapidly activated in response to proinflammatory stimuli, are accumulated in brain lesions of neurodegenerative diseases, such as A...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Libertas Academica
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262374/ https://www.ncbi.nlm.nih.gov/pubmed/25574134 http://dx.doi.org/10.4137/GRSB.S19711 |
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author | Satoh, Jun-ichi Asahina, Naohiro Kitano, Shouta Kino, Yoshihiro |
author_facet | Satoh, Jun-ichi Asahina, Naohiro Kitano, Shouta Kino, Yoshihiro |
author_sort | Satoh, Jun-ichi |
collection | PubMed |
description | Microglia are resident mononuclear phagocytes that play a principal role in the maintenance of normal tissue homeostasis in the central nervous system (CNS). Microglia, rapidly activated in response to proinflammatory stimuli, are accumulated in brain lesions of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. The E26 transformation-specific (ETS) family transcription factor PU.1/Spi1 acts as a master regulator of myeloid and lymphoid development. PU.1-deficient mice show a complete loss of microglia, indicating that PU.1 plays a pivotal role in microgliogenesis. However, the comprehensive profile of PU.1/Spi1 target genes in microglia remains unknown. By analyzing a chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) dataset numbered SRP036026 with the Strand NGS program, we identified 5,264 Spi1 target protein-coding genes in BV2 mouse microglial cells. They included Spi1, Irf8, Runx1, Csf1r, Csf1, Il34, Aif1 (Iba1), Cx3cr1, Trem2, and Tyrobp. By motif analysis, we found that the PU-box consensus sequences were accumulated in the genomic regions surrounding ChIP-Seq peaks. By using pathway analysis tools of bioinformatics, we found that ChIP-Seq-based Spi1 target genes show a significant relationship with diverse pathways essential for normal function of monocytes/macrophages, such as endocytosis, Fc receptor-mediated phagocytosis, and lysosomal degradation. These results suggest that PU.1/Spi1 plays a crucial role in regulation of the genes relevant to specialized functions of microglia. Therefore, aberrant regulation of PU.1 target genes might contribute to the development of neurodegenerative diseases with accumulation of activated microglia. |
format | Online Article Text |
id | pubmed-4262374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Libertas Academica |
record_format | MEDLINE/PubMed |
spelling | pubmed-42623742015-01-08 A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia Satoh, Jun-ichi Asahina, Naohiro Kitano, Shouta Kino, Yoshihiro Gene Regul Syst Bio Original Research Microglia are resident mononuclear phagocytes that play a principal role in the maintenance of normal tissue homeostasis in the central nervous system (CNS). Microglia, rapidly activated in response to proinflammatory stimuli, are accumulated in brain lesions of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. The E26 transformation-specific (ETS) family transcription factor PU.1/Spi1 acts as a master regulator of myeloid and lymphoid development. PU.1-deficient mice show a complete loss of microglia, indicating that PU.1 plays a pivotal role in microgliogenesis. However, the comprehensive profile of PU.1/Spi1 target genes in microglia remains unknown. By analyzing a chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) dataset numbered SRP036026 with the Strand NGS program, we identified 5,264 Spi1 target protein-coding genes in BV2 mouse microglial cells. They included Spi1, Irf8, Runx1, Csf1r, Csf1, Il34, Aif1 (Iba1), Cx3cr1, Trem2, and Tyrobp. By motif analysis, we found that the PU-box consensus sequences were accumulated in the genomic regions surrounding ChIP-Seq peaks. By using pathway analysis tools of bioinformatics, we found that ChIP-Seq-based Spi1 target genes show a significant relationship with diverse pathways essential for normal function of monocytes/macrophages, such as endocytosis, Fc receptor-mediated phagocytosis, and lysosomal degradation. These results suggest that PU.1/Spi1 plays a crucial role in regulation of the genes relevant to specialized functions of microglia. Therefore, aberrant regulation of PU.1 target genes might contribute to the development of neurodegenerative diseases with accumulation of activated microglia. Libertas Academica 2014-12-08 /pmc/articles/PMC4262374/ /pubmed/25574134 http://dx.doi.org/10.4137/GRSB.S19711 Text en © 2014 the author(s), publisher and licensee Libertas Academica Ltd. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License. |
spellingShingle | Original Research Satoh, Jun-ichi Asahina, Naohiro Kitano, Shouta Kino, Yoshihiro A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia |
title | A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia |
title_full | A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia |
title_fullStr | A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia |
title_full_unstemmed | A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia |
title_short | A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia |
title_sort | comprehensive profile of chip-seq-based pu.1/spi1 target genes in microglia |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262374/ https://www.ncbi.nlm.nih.gov/pubmed/25574134 http://dx.doi.org/10.4137/GRSB.S19711 |
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