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Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation
Type 2 immune responses are critical in tissue homeostasis, anti-helminth immunity, and allergy. T helper 2 (Th2) cells produce interleukin-4 (IL-4), IL-5, and IL-13 from the type 2 gene cluster under regulation by transcription factors (TFs) including GATA3. To better understand transcriptional reg...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501989/ https://www.ncbi.nlm.nih.gov/pubmed/37285842 http://dx.doi.org/10.1016/j.immuni.2023.05.010 |
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author | Ferreira, Ana C.F. Szeto, Aydan C.H. Clark, Paula A. Crisp, Alastair Kozik, Patrycja Jolin, Helen E. McKenzie, Andrew N.J. |
author_facet | Ferreira, Ana C.F. Szeto, Aydan C.H. Clark, Paula A. Crisp, Alastair Kozik, Patrycja Jolin, Helen E. McKenzie, Andrew N.J. |
author_sort | Ferreira, Ana C.F. |
collection | PubMed |
description | Type 2 immune responses are critical in tissue homeostasis, anti-helminth immunity, and allergy. T helper 2 (Th2) cells produce interleukin-4 (IL-4), IL-5, and IL-13 from the type 2 gene cluster under regulation by transcription factors (TFs) including GATA3. To better understand transcriptional regulation of Th2 cell differentiation, we performed CRISPR-Cas9 screens targeting 1,131 TFs. We discovered that activity-dependent neuroprotector homeobox protein (ADNP) was indispensable for immune reactions to allergen. Mechanistically, ADNP performed a previously unappreciated role in gene activation, forming a critical bridge in the transition from pioneer TFs to chromatin remodeling by recruiting the helicase CHD4 and ATPase BRG1. Although GATA3 and AP-1 bound the type 2 cytokine locus in the absence of ADNP, they were unable to initiate histone acetylation or DNA accessibility, resulting in highly impaired type 2 cytokine expression. Our results demonstrate an important role for ADNP in promoting immune cell specialization. |
format | Online Article Text |
id | pubmed-10501989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105019892023-09-16 Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation Ferreira, Ana C.F. Szeto, Aydan C.H. Clark, Paula A. Crisp, Alastair Kozik, Patrycja Jolin, Helen E. McKenzie, Andrew N.J. Immunity Article Type 2 immune responses are critical in tissue homeostasis, anti-helminth immunity, and allergy. T helper 2 (Th2) cells produce interleukin-4 (IL-4), IL-5, and IL-13 from the type 2 gene cluster under regulation by transcription factors (TFs) including GATA3. To better understand transcriptional regulation of Th2 cell differentiation, we performed CRISPR-Cas9 screens targeting 1,131 TFs. We discovered that activity-dependent neuroprotector homeobox protein (ADNP) was indispensable for immune reactions to allergen. Mechanistically, ADNP performed a previously unappreciated role in gene activation, forming a critical bridge in the transition from pioneer TFs to chromatin remodeling by recruiting the helicase CHD4 and ATPase BRG1. Although GATA3 and AP-1 bound the type 2 cytokine locus in the absence of ADNP, they were unable to initiate histone acetylation or DNA accessibility, resulting in highly impaired type 2 cytokine expression. Our results demonstrate an important role for ADNP in promoting immune cell specialization. Cell Press 2023-07-11 /pmc/articles/PMC10501989/ /pubmed/37285842 http://dx.doi.org/10.1016/j.immuni.2023.05.010 Text en © 2023 MRC Laboratory of Molecular Biology https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ferreira, Ana C.F. Szeto, Aydan C.H. Clark, Paula A. Crisp, Alastair Kozik, Patrycja Jolin, Helen E. McKenzie, Andrew N.J. Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation |
title | Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation |
title_full | Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation |
title_fullStr | Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation |
title_full_unstemmed | Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation |
title_short | Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation |
title_sort | neuroprotective protein adnp-dependent histone remodeling complex promotes t helper 2 immune cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501989/ https://www.ncbi.nlm.nih.gov/pubmed/37285842 http://dx.doi.org/10.1016/j.immuni.2023.05.010 |
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