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Status |
Public on Jun 10, 2022 |
Title |
NuRD complex recruitment to Thpok mediates CD4+ T cell lineage differentiation |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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 expression of most CD4+- and CD8+-lineage genes. Here, we identify the nucleosome remodeling and deacetylase (NuRD) complex as a novel Thpok cofactor. We locate three amino-acid residues within the Thpok BTB domain that are required for both NuRD binding and Thpok functions, and show that NuRD recruitment recapitulates the functions of the Thpok BTB domain. 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-zinc finger factors, which control the differentiation of most hematopoietic subsets.
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Overall design |
Nuclei were isolated following the recommended protocol from 10X Genomics. Transposition and scATACseq capture was performed with the 10X Chromium Single Cell ATAC Solution (v1.0) , following the manufacturer's recommended protocol
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Contributor(s) |
Chopp LB, Gao Y, Bosselut R |
Citation(s) |
35687698 |
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Submission date |
Mar 30, 2022 |
Last update date |
Sep 09, 2022 |
Contact name |
Remy Bosselut |
E-mail(s) |
bosselur@helix.nih.gov
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Phone |
240-760-6866
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Organization name |
National Cancer Institute, National Institute of Health
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Department |
Laboratory of Immune Cell Biology
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Lab |
Bosselut
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Street address |
9000 Rockville Pike, Building 37
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA821414 |
Supplementary file |
Size |
Download |
File type/resource |
GSE199739_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of BAI, CSV, H5, TBI, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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