Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation.
Immunity
; 56(7): 1468-1484.e7, 2023 07 11.
Article
en En
| MEDLINE
| ID: mdl-37285842
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Histonas
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2023
Tipo del documento:
Article