Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Satoh, Jun-ichi, Asahina, Naohiro, Kitano, Shouta, Kino, Yoshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Libertas Academica 2014
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
_version_ 1782348420320591872
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
work_keys_str_mv AT satohjunichi acomprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT asahinanaohiro acomprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT kitanoshouta acomprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT kinoyoshihiro acomprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT satohjunichi comprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT asahinanaohiro comprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT kitanoshouta comprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia
AT kinoyoshihiro comprehensiveprofileofchipseqbasedpu1spi1targetgenesinmicroglia