Journal of Experimental Medicine, 21 August, 2019，DOI：https://doi.org/10.1084/jem.20182363
Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription
Benyu Liu, Liuliu Yang, Xiaoxiao Zhu, Huimu Li, Pingping Zhu, Jiayi Wu, Tiankun Lu, Luyun He, Nian Liu, Shu Meng, Liang Zhou, Buqing Ye, Yong Tian, Zusen Fan
Innate lymphoid cells (ILCs) play critical roles in defending infections and maintaining mucosal homeostasis. All ILCs arise from common lymphoid progenitors (CLPs) in bone marrow. However, how CLPs stratify and differentiate into ILC lineages remains elusive. Here, we showed that Yeats4 is highly expressed in ILCs and their progenitors. Yeats4 conditional KO in the hematopoietic system causes decreased numbers of ILCs and impairs their effector functions. Moreover, Yeats4 regulates α4β7+ CLP differentiation toward common helper ILC progenitors (CHILPs). Mechanistically, Yeats4 recruits the Dot1l–RNA Pol II complex onto Lmo4 promoter through recognizing H3K27ac modification to initiate Lmo4 transcription in α4β7+ CLPs. Additionally, Lmo4 deficiency also impairs ILC lineage differentiation and their effector functions. Collectively, the Yeats4–Lmo4 axis is required for ILC lineage commitment.