BRD7 as key factor in PBAF complex assembly and CD8+ T cell differentiation
Feng Huang, Yingtong Lin, Yidan Qiao, Yaochang Yuan, Zhihan Zhong, Baohong Luo, Yating Wu, Jun Liu, Jingliang Chen, Wanying Zhang, Hui Zhang, Bingfeng Liu
Feng Huang, Yingtong Lin, Yidan Qiao, Yaochang Yuan, Zhihan Zhong, Baohong Luo, Yating Wu, Jun Liu, Jingliang Chen, Wanying Zhang, Hui Zhang, Bingfeng Liu
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Research Article Immunology Infectious disease

BRD7 as key factor in PBAF complex assembly and CD8+ T cell differentiation

Abstract

Upon infection, naive CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this process have been demonstrated, the regulatory role of chromatin remodeling system in this process remains largely unknown. Here we show that BRD7, a component of the polybromo-associated BAF complex (PBAF), was required for naive CD8+ T cells to differentiate into functional short-lived effector cells (SLECs) in response to acute infections caused by influenza virus or lymphocytic choriomeningitis virus (LCMV). BRD7 deficiency in CD8+ T cells resulted in profound defects in effector population and functions, thereby impairing viral clearance and host recovery. Further mechanical studies indicate that the expression of BRD7 significantly turned to high from naive CD8+ T cells to effector cells, which bridged BRG1 and PBRM1 to the core module of PBAF complex, consequently facilitating the assembly of PBAF complex rather than BAF complex in the effector cells. The PBAF complex changed the chromatin accessibility at the loci of Tbx21 gene and upregulated its expression, leading to the maturation of effector T cells. Our research demonstrates that BRD7 and the PBAF complex are key in CD8+ T cell development and present a significant target for advancing immune therapies.

Authors

Feng Huang, Yingtong Lin, Yidan Qiao, Yaochang Yuan, Zhihan Zhong, Baohong Luo, Yating Wu, Jun Liu, Jingliang Chen, Wanying Zhang, Hui Zhang, Bingfeng Liu

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Figure 7

BRD7 functions as a bridge for PBAF complex to efficiently assemble in effector CD8+ T cells.

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BRD7 functions as a bridge for PBAF complex to efficiently assemble in e...
(A) MS analysis of BRG1-associated proteins in naive OT-I CD8+ T (n = 2) or effector OT-I CD8+ T cells (n = 2) from OT-I mice infected with PR8-OVA at day 8 p.i. (B) Venn diagram showing the overlap of components. List 1: Reported components of BAF complex. List 2: Identified components of BAF complex from naive cells in A. List 3: Reported BAF-specific components. List 4: Identified BAF-specific from naive cells in A. (C) SWI/SNF components from naive T cells in A were clustered with STRING analysis. (D) Venn diagram showing the overlap of components. List 1: Reported components of PBAF complex. List 2: Identified components of PBAF complex from effector cells in A. List 3: Reported PBAF-specific components. List 4: Identified PBAF-specific from effector cells in A. (E) SWI/SNF components from effector cells in A were clustered with STRING analysis. (F) Co-IP of BRG1-associated proteins in naive CD8+ T (n = 2) or effector CD8+ T cells (n = 2) from OT-I mice infected with PR8-OVA. (G) ChIP (n = 3) shows the deposition of BRG1 at the promoter regions of Tbx21 loci. (H and I) The mRNA expression (n = 3) of Brg1 and Tbx21 of OT-I T cells of shRNA was analyzed 8 days after transfer into recipient mice infected with PR8-OVA virus. (J) Co-IP of BRG1 in BRD7 WT and BRD7-deficient CD8+ T cells from OT-I mice infected with PR8-OVA at day 8 p.i. (K and L) ChIP (n = 3) shows the deposition of BRG1 and SMARCC1 at the promoter of Tbx21 in BRD7 WT and BRD7-deficient CD8+ T cells from OT-I mice infected with PR8-OVA at day 8 p.i. Data are shown as mean ± SEM. *P < 0.05 and ***P < 0.001 (2-tailed Student’s t test). Data are representative of 2 independent experiments.