NuRD complex recruitment to Thpok mediates CD4 + T cell lineage differentiation.

Autor:	Gao Y; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Zamisch M; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Vacchio M; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Chopp L; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.; Immunology Graduate Group, University of Pennsylvania Medical School, Philadelphia, PA, USA., Ciucci T; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Paine EL; Collaborative Protein Technology Resource, Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Lyons GC; Collaborative Protein Technology Resource, Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Nie J; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Xiao Q; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Zvezdova E; Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA., Love PE; Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA., Vinson CR; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Jenkins LM; Immunology Graduate Group, University of Pennsylvania Medical School, Philadelphia, PA, USA., Bosselut R; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2022 Jun 10; Vol. 7 (72), pp. eabn5917. Date of Electronic Publication: 2022 Jun 10.
DOI:	10.1126/sciimmunol.abn5917
Abstrakt:	Although BTB-zinc finger (BTB-ZF) transcription factors control the differentiation of multiple hematopoietic and immune lineages, how they function is poorly understood. The BTB-ZF factor Thpok controls intrathymic CD4 + T cell development and the expression of most CD4 + and CD8 + lineage genes. Here, we identify the nucleosome remodeling and deacetylase (NuRD) complex as a critical Thpok cofactor. Using mass spectrometry and coimmunoprecipitation in primary T cells, we show that Thpok binds NuRD components independently of DNA association. We locate three amino acid residues within the Thpok BTB domain that are required for both NuRD binding and Thpok functions. Conversely, a chimeric protein merging the NuRD component Mta2 to a BTB-less version of Thpok supports CD4 + T cell development, indicating that NuRD recruitment recapitulates the functions of the Thpok BTB domain. We found that NuRD mediates Thpok repression of CD8 + lineage genes, including the transcription factor Runx3 , but is dispensable for Cd4 expression. We show that these functions cannot be performed by the BTB domain of the Thpok-related factor Bcl6, which fails to bind NuRD. Thus, cofactor binding critically contributes to the functional specificity of BTB-ZF factors, which control the differentiation of most hematopoietic subsets.
Databáze:	MEDLINE
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