The eukaryotic genome is three‐dimensionally segregated into discrete globules of topologically associating domains (TADs), within which numerous cis‐regulatory elements such as enhancers and promoters interact to regulate gene expression. In this study, we identify a T‐cell‐specific sub‐TAD containing the Gata3 locus, and reveal a previously uncharacterized long noncoding RNA (Dreg1) within a distant enhancer lying approximately 280 kb downstream of Gata3. Dreg1 expression is highly correlated with that of Gata3 during early immune system development and T helper type 2 cell differentiation. Inhibition and overexpression of Dreg1 suggest that it may be involved in the establishment, but not in the maintenance of Gata3 expression. Overall, we propose that Dreg1 is a novel regulator of Gata3 and may inform therapeutic strategies in diseases such allergy and lymphoma, where Gata3 has a pathological role.

中文翻译：

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长链非编码 RNA Dreg1 作为 Gata3 新型调节因子的鉴定和表征

真核基因组被三维分离成拓扑相关域 (TAD) 的离散小球，其中许多顺式调节元件如增强子和启动子相互作用以调节基因表达。在这项研究中，我们鉴定了一个包含Gata3基因座的 T 细胞特异性子 TAD ，并在位于Gata3下游约 280 kb 的远处增强子中揭示了以前未表征的长非编码 RNA ( Dreg1 ) 。在早期免疫系统发育和 T 辅助细胞 2 型分化过程中，Dreg1 表达与 Gata3 的表达高度相关。Dreg1 的抑制和过表达表明它可能参与建立，但不参与Gata3表达的维持。总的来说，我们认为Dreg1是Gata3的新型调节剂，可以为过敏和淋巴瘤等疾病的治疗策略提供信息，其中Gata3具有病理学作用。