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; En Jun 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

doi:10.1016/j.immuni.2017.08.012

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, En Jun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C. Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku KambayashiIgor E. Brodsky, John J. O'Shea, E. John Wherry, Loyal A. Goff, John L. Rinn, Adam Williams, Richard A. Flavell, Jorge Henao-Mejia

School of Medicine

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

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. Mowel et al. find that the locus demarcated by the lncRNA Rroid controls the function and lineage identity of group 1 ILCs by promoting the expression of the transcriptional regulator Id2 in response to IL-15. Their findings demonstrate a critical role for non-coding regulatory elements responsive to unique extracellular cues in the function and homeostasis of individual ILC subsets.

Original language	English (US)
Pages (from-to)	435-449.e8
Journal	Immunity
Volume	47
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2017.08.012
State	Published - Sep 19 2017

Keywords

ILC1
Id2
innate lymphoid cells
lineage identity
lncRNA
transcriptional regulation

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2017.08.012

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Mowel, W. K., McCright, S. J., Kotzin, J. J., Collet, M. A., Uyar, A., Chen, X., DeLaney, A., Spencer, S. P., Virtue, A. T., Yang, E. J., Villarino, A., Kurachi, M., Dunagin, M. C., Pritchard, G. H., Stein, J., Hughes, C., Fonseca-Pereira, D., Veiga-Fernandes, H., Raj, A., ... Henao-Mejia, J. (2017). Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA. Immunity, 47(3), 435-449.e8. https://doi.org/10.1016/j.immuni.2017.08.012

Mowel, WK, McCright, SJ, Kotzin, JJ, Collet, MA, Uyar, A, Chen, X, DeLaney, A, Spencer, SP, Virtue, AT, Yang, EJ, Villarino, A, Kurachi, M, Dunagin, MC, Pritchard, GH, Stein, J, Hughes, C, Fonseca-Pereira, D, Veiga-Fernandes, H, Raj, A, Kambayashi, T, Brodsky, IE, O'Shea, JJ, Wherry, EJ, Goff, LA, Rinn, JL, Williams, A, Flavell, RA & Henao-Mejia, J 2017, 'Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA', Immunity, vol. 47, no. 3, pp. 435-449.e8. https://doi.org/10.1016/j.immuni.2017.08.012

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

abstract = "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. Mowel et al. find that the locus demarcated by the lncRNA Rroid controls the function and lineage identity of group 1 ILCs by promoting the expression of the transcriptional regulator Id2 in response to IL-15. Their findings demonstrate a critical role for non-coding regulatory elements responsive to unique extracellular cues in the function and homeostasis of individual ILC subsets.",

keywords = "ILC1, Id2, innate lymphoid cells, lineage identity, lncRNA, transcriptional regulation",

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

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doi = "10.1016/j.immuni.2017.08.012",

language = "English (US)",

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T1 - Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA

AU - Mowel, Walter K.

AU - McCright, Sam J.

AU - Kotzin, Jonathan J.

AU - Collet, Magalie A.

AU - Uyar, Asli

AU - Chen, Xin

AU - DeLaney, Alexandra

AU - Spencer, Sean P.

AU - Virtue, Anthony T.

AU - Yang, En Jun

AU - Villarino, Alejandro

AU - Kurachi, Makoto

AU - Dunagin, Margaret C.

AU - Pritchard, Gretchen Harms

AU - Stein, Judith

AU - Hughes, Cynthia

AU - Fonseca-Pereira, Diogo

AU - Veiga-Fernandes, Henrique

AU - Raj, Arjun

AU - Kambayashi, Taku

AU - Brodsky, Igor E.

AU - O'Shea, John J.

AU - Wherry, E. John

AU - Goff, Loyal A.

AU - Rinn, John L.

AU - Williams, Adam

AU - Flavell, Richard A.

AU - Henao-Mejia, Jorge

PY - 2017/9/19

Y1 - 2017/9/19

N2 - 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. Mowel et al. find that the locus demarcated by the lncRNA Rroid controls the function and lineage identity of group 1 ILCs by promoting the expression of the transcriptional regulator Id2 in response to IL-15. Their findings demonstrate a critical role for non-coding regulatory elements responsive to unique extracellular cues in the function and homeostasis of individual ILC subsets.

AB - 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. Mowel et al. find that the locus demarcated by the lncRNA Rroid controls the function and lineage identity of group 1 ILCs by promoting the expression of the transcriptional regulator Id2 in response to IL-15. Their findings demonstrate a critical role for non-coding regulatory elements responsive to unique extracellular cues in the function and homeostasis of individual ILC subsets.

KW - ILC1

KW - Id2

KW - innate lymphoid cells

KW - lineage identity

KW - lncRNA

KW - transcriptional regulation

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DO - 10.1016/j.immuni.2017.08.012

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AN - SCOPUS:85031753412

SN - 1074-7613

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SP - 435-449.e8

JO - Immunity

JF - Immunity

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ER -

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

Abstract

Keywords

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