Title: | Transcription factor Achaete-Scute homologue 2 initiates T follicular helper cell development [ChIP-Seq]
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dateReleased: |
01-01-2014
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description: |
In immune responses, activated T cells migrate to B cell follicles and develop to T follicular helper (Tfh) cells, a new subset of CD4+ T cells specialized in providing help to B lymphocytes in the induction of germinal centers 1-3. Although Bcl6 has been shown to be essential in Tfh cell function, it may not regulate the initial migration of T cells 4 or the induction of Tfh program as exampled by CXCR5 upregulation 5. Here, we show that the Achaete-Scute homologue 2 (Ascl2) gene that encodes a basic helix-loop-helix (bHLH) transcription factor 6, is selectively upregulated in its expression in Tfh cells. Ectopic expression of Ascl2 uniquely upregulates CXCR5 but not Bcl6 and downregulates CCR7 expression in T cells in vitro and accelerates T cell migration to the follicles and Tfh cell development in vivo. Combined transcriptome profiling and genome-wide occupancy analysis indicate that Ascl2 directly regulates Tfh-related genes while inhibits expression of Th1 and Th17 genes. Acute deletion of Ascl2 as well as blockade of its function with the Id3 protein in peripheral CD4+ T cells results in a failure in Tfh cell development and the germinal center response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances Tfh cell generation. Thus, Ascl2 critically and directly initiates Tfh cell development. Decide Ascl2 binding sites in CD4+ T cells
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privacy: |
not applicable
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aggregation: |
instance of dataset
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ID: |
E-GEOD-52839
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refinement: |
raw
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alternateIdentifiers: |
52839
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keywords: |
functional genomics
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dateModified: |
05-31-2014
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availability: |
available
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types: |
gene expression
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name: |
Mus musculus
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-52839/E-GEOD-52839.raw.1.zip![]() |
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ArrayExpress
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gzip compressed
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TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-52839/E-GEOD-52839.processed.1.zip |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52839 |
storedIn: |
Gene Expression Omnibus
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qualifier: |
not compressed
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format: |
HTML
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accessType: |
landing page
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primary: |
true
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authentication: |
none
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authorization: |
none
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abbreviation: |
EBI
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homePage: | http://www.ebi.ac.uk/ |
ID: |
SCR:004727
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name: |
European Bioinformatics Institute
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homePage: | https://www.ebi.ac.uk/arrayexpress/ |
ID: |
SCR:002964
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name: |
ArrayExpress
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