title: Chromatin remodeling complex NURF regulates thymocyte maturation.
abstract: The maturation of T cells requires signaling from both cytokine and T-cell receptors to gene targets in chromatin, but how chromatin architecture influences this process is largely unknown. Here we show that thymocyte maturation post-positive selection is dependent on the nucleosome remodeling factor (NURF). Depletion of Bptf (bromodomain PHD finger transcription factor), the largest NURF subunit, in conditional mouse mutants results in developmental arrest beyond the CD4(+) CD8(int) stage without affecting cellular proliferation, cellular apoptosis, or coreceptor gene expression. In the Bptf mutant, specific subsets of genes important for thymocyte development show aberrant expression. We also observed defects in DNase I-hypersensitive chromatin structures at Egr1, a prototypical Bptf-dependent gene that is required for efficient thymocyte development. Moreover, chromatin binding of the sequence-specific factor Srf (serum response factor) to Egr1 regulatory sites is dependent on Bptf function. Physical interactions between NURF and Srf suggest a model in which Srf recruits NURF to facilitate transcription factor binding at Bptf-dependent genes. These findings provide evidence for causal connections between NURF, transcription factor occupancy, and gene regulation during thymocyte development.
authors.affiliation: Laboratory of Biochemistry and Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jwlandry2@vcu.edu
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Landry
authors.forename: Subhadra
authors.initials: S
authors.lastname: Banerjee
authors.forename: Barbara
authors.initials: B
authors.lastname: Taylor
authors.forename: Peter D
authors.initials: PD
authors.lastname: Aplan
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
authors.forename: Carl
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D034961:Antigens, Nuclear; D002843:Chromatin; D004247:DNA; D051766:Early Growth Response Protein 1; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C486109:Egr1 protein, mouse; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins