title: RUNX transcription factor-mediated association of Cd4 and Cd8 enables coordinate gene regulation.
abstract: T cell fate is associated with mutually exclusive expression of CD4 or CD8 in helper and cytotoxic T cells, respectively. How expression of one locus is temporally coordinated with repression of the other has been a long-standing enigma, though we know RUNX transcription factors activate the Cd8 locus, silence the Cd4 locus, and repress the Zbtb7b locus (encoding the transcription factor ThPOK), which is required for CD4 expression. Here we found that nuclear organization was altered by interplay among members of this transcription factor circuitry: RUNX binding mediated association of Cd4 and Cd8 whereas ThPOK binding kept the loci apart. Moreover, targeted deletions within Cd4 modulated CD8 expression and pericentromeric repositioning of Cd8. Communication between Cd4 and Cd8 thus appears to enable long-range epigenetic regulation to ensure that expression of one excludes the other in mature CD4 or CD8 single-positive (SP) cells.
authors: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors: Amélie
authors: A
authors: Collins
authors: Susannah L
authors: SL
authors: Hewitt
authors: Julie
authors: J
authors: Chaumeil
authors: Maclean
authors: M
authors: Sellars
authors: Mariann
authors: M
authors: Micsinai
authors: Jeanne
authors: J
authors: Allinne
authors: Fabio
authors: F
authors: Parisi
authors: Elphège P
authors: EP
authors: Nora
authors: Dan J
authors: DJ
authors: Bolland
authors: Anne E
authors: AE
authors: Corcoran
authors: Yuval
authors: Y
authors: Kluger
authors: Remy
authors: R
authors: Bosselut
authors: Wilfried
authors: W
authors: Ellmeier
authors: Mark M W
authors: MM
authors: Chong
authors: Dan R
authors: DR
authors: Littman
authors: Jane A
authors: JA
authors: Skok
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D050657:Core Binding Factor alpha Subunits / Q000276:immunology*; D057890:Epigenomics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D050657:Core Binding Factor alpha Subunits