RUNX Transcription Factor-Mediated Association of Cd4 and Cd8 Enables Coordinate Gene Regulation

被引：31

作者：

Collins, Amelie ^{[2
]}

Hewitt, Susannah L. ^{[1
]}

Chaumeil, Julie ^{[1
]}

Sellars, MacLean ^{[2
]}

Micsinai, Mariann ^{[1
,3
,4
,5
]}

Allinne, Jeanne ^{[1
]}

Parisi, Fabio ^{[1
,5
]}

Nora, Elphege P. ^{[6
]}

Bolland, Dan J. ^{[7
]}

Corcoran, Anne E. ^{[7
]}

Kluger, Yuval ^{[1
,5
]}

Bosselut, Remy ^{[8
]}

Ellmeier, Wilfried ^{[9
]}

Chong, Mark M. W. ^{[2
]}

Littman, Dan R. ^{[2
,11
]}

Skok, Jane A. ^{[1
,10
]}

机构：

[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[2] NYU, Sch Med, Kimmel Ctr Biol & Med, Mol Pathogenesis Program,Skirball Inst, New York, NY 10016 USA

[3] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA

[4] NYU, Sch Med, Inst Canc, New York, NY 10016 USA

[5] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06520 USA

[6] Inst Curie, CNRS, INSERM, UMR3215,U934, F-75724 Paris 05, France

[7] Babraham Inst, Cambridge CB22 3AT, England

[8] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[9] Med Univ Vienna, Inst Immunol, Div Immunobiol, A-1090 Vienna, Austria

[10] UCL, Dept Immunol & Mol Pathol, Div Infect & Immun, London W1T 4JF, England

[11] UCL, Howard Hughes Med Inst, London W1T 4JF, England

来源：

IMMUNITY | 2011年 / 34卷 / 03期

基金：

美国国家科学基金会; 奥地利科学基金会; 英国生物技术与生命科学研究理事会;

关键词：

T-CELL LINEAGE; THYMOCYTE DIFFERENTIATION; LYMPHOCYTE DEVELOPMENT; IMMUNOGLOBULIN LOCI; X-INACTIVATION; B-CELLS; EXPRESSION; COMMITMENT; SILENCER; ENHANCER;

D O I：

10.1016/j.immuni.2011.03.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：303 / 314

页数：12

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