Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation

Xindong Liu, Huiping Lu, Tingting Chen, Kalyan C. Nallaparaju, Xiaowei Yan, Shinya Tanaka, Kenji Ichiyama, Xia Zhang, Li Zhang, Xiaofeng Wen, Qiang Tian, Xiu wu Bian, Wei Jin, Lai Wei, Chen Dong

Research output: Contribution to journalArticle

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Abstract

T follicular helper (Tfh) cell is a unique T cell subset specialized in promoting humoral immunity. B-cell lymphoma 6 protein (Bcl6) has been identified as an obligatory transcription factor in Tfh cells; however, the molecular mechanism underlying Bcl6 function remains largely unknown. Here, we defined Bcl6 target genes in Tfh cells by analyzing genome-wide Bcl6 occupancy together with transcriptome profiling. With consensus sequences being different from those in Th9, B cells, and macrophages, Bcl6 binding in Tfh cell was closely associated with a decrease in 5-hydroxymethylcytosine (5hmC). Importantly, Bcl6 promoted Tfh cell differentiation through antagonizing IL-7R (CD127)/signal transducer and activator of transcription (STAT) 5 axis; deletion of the Bcl6 gene in T cells resulted in enhanced IL-7R-STAT5 signaling and substantial expansion of CD127hi non-Tfh cells. Thus, our study systemically examines Bcl6-controlled regulatory networks and provides important insights into Bcl6's biological functions in Tfh cells.

Original languageEnglish
Pages (from-to)1735-1747
Number of pages13
JournalCell Reports
Volume14
Issue number7
DOIs
Publication statusPublished - Feb 23 2016

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Proto-Oncogene Proteins c-bcl-6
Cell Differentiation
Helper-Inducer T-Lymphocytes
Genes
Genome
T-cells
STAT5 Transcription Factor
Macrophages
Consensus Sequence
T-Lymphocyte Subsets
Gene Expression Profiling
Humoral Immunity
Protein Binding

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation. / Liu, Xindong; Lu, Huiping; Chen, Tingting; Nallaparaju, Kalyan C.; Yan, Xiaowei; Tanaka, Shinya; Ichiyama, Kenji; Zhang, Xia; Zhang, Li; Wen, Xiaofeng; Tian, Qiang; Bian, Xiu wu; Jin, Wei; Wei, Lai; Dong, Chen.

In: Cell Reports, Vol. 14, No. 7, 23.02.2016, p. 1735-1747.

Research output: Contribution to journalArticle

Liu, X, Lu, H, Chen, T, Nallaparaju, KC, Yan, X, Tanaka, S, Ichiyama, K, Zhang, X, Zhang, L, Wen, X, Tian, Q, Bian, XW, Jin, W, Wei, L & Dong, C 2016, 'Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation', Cell Reports, vol. 14, no. 7, pp. 1735-1747. https://doi.org/10.1016/j.celrep.2016.01.038
Liu, Xindong ; Lu, Huiping ; Chen, Tingting ; Nallaparaju, Kalyan C. ; Yan, Xiaowei ; Tanaka, Shinya ; Ichiyama, Kenji ; Zhang, Xia ; Zhang, Li ; Wen, Xiaofeng ; Tian, Qiang ; Bian, Xiu wu ; Jin, Wei ; Wei, Lai ; Dong, Chen. / Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation. In: Cell Reports. 2016 ; Vol. 14, No. 7. pp. 1735-1747.
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