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The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration.

Publication ,  Journal Article
Callen, E; Faryabi, RB; Luckey, M; Hao, B; Daniel, JA; Yang, W; Sun, H-W; Dressler, G; Peng, W; Chi, H; Ge, K; Krangel, MS; Park, J-H; Nussenzweig, A
Published in: Immunity
December 14, 2012

Histone 3 lysine 4 trimethylation (H3K4me3) is associated with promoters of active genes and found at hot spots for DNA recombination. Here we have shown that PAXIP1 (also known as PTIP), a protein associated with MLL3 and MLL4 methyltransferase and the DNA damage response, regulates RAG-mediated cleavage and repair during V(D)J recombination in CD4(+) CD8(+) DP thymocytes. Loss of PAXIP1 in developing thymocytes diminished Jα H3K4me3 and germline transcription, suppressed double strand break formation at 3' Jα segments, but resulted in accumulation of unresolved T cell receptor α-chain gene (Tcra) breaks. Moreover, PAXIP1 was essential for release of mature single positive (SP) αβ T cells from the thymus through transcriptional activation of sphingosine-1-phosphate receptor S1pr1 as well as for natural killer T cell development. Thus, in addition to maintaining genome integrity during Tcra rearrangements, PAXIP1 controls distinct transcriptional programs during DP differentiation necessary for Tcra locus accessibility, licensing mature thymocytes for trafficking and natural killer T cell development.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

December 14, 2012

Volume

37

Issue

6

Start / End Page

971 / 985

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Thymocytes
  • T-Lymphocytes
  • Sphingosine-1-Phosphate Receptors
  • Recombination, Genetic
  • Receptors, Lysosphingolipid
  • Receptors, Antigen, T-Cell, alpha-beta
  • Promoter Regions, Genetic
  • Nuclear Proteins
  • Natural Killer T-Cells
 

Citation

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Callen, E., Faryabi, R. B., Luckey, M., Hao, B., Daniel, J. A., Yang, W., … Nussenzweig, A. (2012). The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity, 37(6), 971–985. https://doi.org/10.1016/j.immuni.2012.10.007
Callen, Elsa, Robert B. Faryabi, Megan Luckey, Bingtao Hao, Jeremy A. Daniel, Wenjing Yang, Hong-Wei Sun, et al. “The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration.Immunity 37, no. 6 (December 14, 2012): 971–85. https://doi.org/10.1016/j.immuni.2012.10.007.
Callen E, Faryabi RB, Luckey M, Hao B, Daniel JA, Yang W, et al. The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity. 2012 Dec 14;37(6):971–85.
Callen, Elsa, et al. “The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration.Immunity, vol. 37, no. 6, Dec. 2012, pp. 971–85. Pubmed, doi:10.1016/j.immuni.2012.10.007.
Callen E, Faryabi RB, Luckey M, Hao B, Daniel JA, Yang W, Sun H-W, Dressler G, Peng W, Chi H, Ge K, Krangel MS, Park J-H, Nussenzweig A. The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity. 2012 Dec 14;37(6):971–985.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

December 14, 2012

Volume

37

Issue

6

Start / End Page

971 / 985

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Thymocytes
  • T-Lymphocytes
  • Sphingosine-1-Phosphate Receptors
  • Recombination, Genetic
  • Receptors, Lysosphingolipid
  • Receptors, Antigen, T-Cell, alpha-beta
  • Promoter Regions, Genetic
  • Nuclear Proteins
  • Natural Killer T-Cells