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ILC1 lineage identity is determined by a cis-regulatory element marked by a novel lncRNA

ABSTRACT: ILC1 lineage identity is determined by a cis-regulatory element marked by a novel lncRNA

PROVIDER: PRJNA394398 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5828150.fastq.gz	Fastqsanger.gz
	SRR5828151.fastq.gz	Fastqsanger.gz
	SRR5828152.fastq.gz	Fastqsanger.gz
	SRR5828153.fastq.gz	Fastqsanger.gz
	SRR5828154_1.fastq.gz	Fastqsanger.gz

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ILC1 lineage identity is determined by a cis-regulatory element marked by a novel lncRNA [RNA-seq]

Project description:Innate lymphoid cells (ILCs) comprise three groups of recently identified tissue resident immune cell lineages that play critical roles in protective immune responses and tissue homeostasis. While significant progress has been made in defining the key protein mediators of ILC development and function, how cis-acting epigenetic regulatory elements or long non-coding RNAs (lncRNAs) regulate ILCs is unknown. Herein, we describe a cis-regulatory element demarcated by a novel lncRNA that controls the maturation, function and lineage identity of group 1 ILCs while being dispensable for early ILC development and homeostasis of mature ILC2s and ILC3s. We named this ILC1-restricted lncRNA Rroid. The Rroid locus controls the functional specification and lineage identity of ILC1 by promoting chromatin accessibility and STAT5 deposition at the promoter of its neighboring gene, Id2, in response to the ILC1-specific cytokine IL-15.

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ILC1 lineage identity is determined by a cis-regulatory element marked by a novel lncRNA

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Identification of a novel Aire-regulating cis-regulatory element using H3K27ac ChIP-seq

Project description:Thymic central tolerance is essential to preventing autoimmunity. In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an essential role in this process by driving the expression of a diverse set of tissue-specific antigens (TSAs), which are presented and help tolerize self-reactive thymocytes. Interestingly, Aire has a highly tissue-restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (eTACs) known to express detectable levels in adults. Despite this high level of tissue specificity, the cis-regulatory elements that control Aire expression have remained obscure. We used sequence conservation analysis and ChIP-seq against the enhancer-associated histone mark H3K27ac to identify a candidate Aire cis-regulatory element. There is enrichment of H3K27ac near this element, ACNS1, in mTECs and the element also has characteristics of being NF-ÎºB-responsive. Finally, we find that this element is essential for Aire expression in vivo and necessary to prevent spontaneous autoimmunity, reflecting the importance of this regulatory DNA element in promoting immune tolerance. Two experimental groups (GFP neg mTECs and GFP pos mTECs), each with three samples, and one control sample (D10 Th2 cells).

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