Dataset Information

A chromatin-regulated biphasic circuit coordinates IL1B-mediated inflammation

ABSTRACT: Inflammation is characterized by a biphasic cycle consisting initially of a pro-inflammatory phase which is subsequently resolved by anti-inflammatory processes. The coordination of these two disparate states needs to be highly controlled, suggesting that the regulation of the cytokines that drive these processes are intimately linked. Interleukin-1 beta (IL1B) is a master regulator of pro-inflammation and is encoded within the same topologically associated domain (TAD) as interleukin-37 (IL37). IL37 has recently emerged as a powerful anti-inflammatory cytokine which diametrically opposes the function of IL1B. Within this TAD, we identified a novel long non-coding RNA called AMANZI which negatively regulates IL1B expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced pro-inflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL1B and IL37, thereby regulating two functionally opposed states of inflammation from within a single TAD.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Cathrin Graewe

LAB HEAD: Musa M. Mhlanga

PROVIDER: PXD045971 | Pride | 2023-10-27

REPOSITORIES: Pride

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			Action	DRS
	20210326_Exploris1_SA_CG_EF_Amanzi_A_modified_1.raw	Raw
	20210326_Exploris1_SA_CG_EF_Amanzi_A_modified_2.raw	Raw
	20210326_Exploris1_SA_CG_EF_Amanzi_A_modified_3.raw	Raw
	20210326_Exploris1_SA_CG_EF_Amanzi_A_unmodified_1.raw	Raw
	20210326_Exploris1_SA_CG_EF_Amanzi_A_unmodified_2.raw	Raw

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A chromatin-regulated biphasic circuit coordinates IL1B-mediated inflammation

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