학술행사/세미나 안내 및 신청
Transcriptional control of type 1 dendritic cell development
연사
김선경 교수 (아주대학교)
세미나개최일
2024. 12. 2 (월) 오후 4시. 20동 103호
작성자
정연석
작성일
2024-11-16
조회
302
Transcriptional control of type 1 dendritic cell development
via Irf8 superenhancer
Sunkyung Kim Ph.D.
Classical type 1 dendritic cell (cDC1) plays an essential role to activate immune responses against tumors and viruses. Transcription factor IRF8 determines cDC1 fate specification in the common dendritic cell progenitor (CDP)s and maintain cDC1 identity. Irf8 is the top ranked super-enhancer in cDC1s and contains three constituent enhancers acting sequentially at different stages of cDC1 development. The enhancer placed at 56 kilobases (kb) downstream of Irf8 transcription start site (+56 kb) acts in monocyte dendritic cell progenitor (MDP)s, while the +41 kb enhancer becomes active during transition of MDPs into CDPs and is required for pre-cDC1 specification in CDPs. The BATF3-dependent +32 kb enhancer becomes active only after pre-cDC1 specification and maintains high level of Irf8 expression in mature cDC1. The activity at the +56 kb enhancer is required for subsequent activation of the +41 and +32 kb enhancers located in cis. Likewise, activity at the +32 kb enhancer is strictly dependent on the preceding +41 kb enhancer, driving high levels of IRF8 expression during cDC1 maturation. In summary, cDC1 development and the maintenance of cell identity are coordinated by cis interactions among the developmental stage-specific enhancers within the Irf8 locus.
via Irf8 superenhancer
Sunkyung Kim Ph.D.
Classical type 1 dendritic cell (cDC1) plays an essential role to activate immune responses against tumors and viruses. Transcription factor IRF8 determines cDC1 fate specification in the common dendritic cell progenitor (CDP)s and maintain cDC1 identity. Irf8 is the top ranked super-enhancer in cDC1s and contains three constituent enhancers acting sequentially at different stages of cDC1 development. The enhancer placed at 56 kilobases (kb) downstream of Irf8 transcription start site (+56 kb) acts in monocyte dendritic cell progenitor (MDP)s, while the +41 kb enhancer becomes active during transition of MDPs into CDPs and is required for pre-cDC1 specification in CDPs. The BATF3-dependent +32 kb enhancer becomes active only after pre-cDC1 specification and maintains high level of Irf8 expression in mature cDC1. The activity at the +56 kb enhancer is required for subsequent activation of the +41 and +32 kb enhancers located in cis. Likewise, activity at the +32 kb enhancer is strictly dependent on the preceding +41 kb enhancer, driving high levels of IRF8 expression during cDC1 maturation. In summary, cDC1 development and the maintenance of cell identity are coordinated by cis interactions among the developmental stage-specific enhancers within the Irf8 locus.
