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Norway

PMID:28930659  

Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA.

Walter K Mowel | Sam J McCright | Jonathan J Kotzin | Magalie A Collet | Asli Uyar | Xin Chen | Alexandra DeLaney | Sean P Spencer | Anthony T Virtue | EnJun Yang | Alejandro Villarino | Makoto Kurachi | Margaret C Dunagin | Gretchen Harms Pritchard | Judith Stein | Cynthia Hughes | Diogo Fonseca-Pereira | Henrique Veiga-Fernandes | Arjun Raj | Taku Kambayashi | Igor E Brodsky | John J O'Shea | E John Wherry | Loyal A Goff | John L Rinn | Adam Williams | Richard A Flavell | Jorge Henao-Mejia
Immunity | 2017

Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs. Moreover, the Rroid locus, but not the lncRNA itself, controlled the identity and function of ILC1s by promoting chromatin accessibility and deposition of STAT5 at the promoter of Id2 in response to interleukin (IL)-15. Thus, non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs.

Pubmed ID: 28930659

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007780
  • Agency: NIAID NIH HHS, United States
    Id: F31 AI124538
  • Agency: NIDDK NIH HHS, United States
    Id: F30 DK094708
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI055428
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001863
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL136572
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI128060
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI128530
  • Agency: NIH HHS, United States
    Id: DP2 OD008514
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI110776
  • Agency: NIDDK NIH HHS, United States
    Id: R21 DK111755
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI103062
  • Agency: NIBIB NIH HHS, United States
    Id: R33 EB019767

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GraphPad (tool)

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RRID:SCR_008520

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BD Biosciences (tool)

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