Ford A M, Bennett C A, Healy L E, Navarro E, Spooncer E, Greaves M F
Leukaemia Research Fund Centre, Chester Beatty Laboratories, London, United Kingdom.
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3424-8. doi: 10.1073/pnas.89.8.3424.
Multipotential interleukin 3-dependent non-immortalized murine hemopoietic progenitor cells have DNase I-hypersensitive sites in the immunoglobulin heavy-chain and CD3 delta enhancers and transcribe germ-line T-cell antigen receptor gamma-chain (TCR gamma), but not IgM or TCR beta, genes. Induction of myeloid differentiation in these cells clones down expression and/or transcriptional accessibility of the immunoglobulin heavy-chain and TCR gamma genes. The CD3 delta enhancer region remains DNase I-hypersensitive but closes down in B cells. In embryonic stem cells and pan-mesodermal cells, these genes or enhancer regions are neither expressed nor DNase I-hypersensitive. These data suggest that lineage potential may be programmed, at least in part, by alterations in the accessibility or conformation of regulatory regions of genes and that some promiscuity of gene expression and/or accessibility can precede lineage commitment and maturation in progenitor cells induced to self-renew by interleukin 3.
多能白细胞介素3依赖的未永生化小鼠造血祖细胞在免疫球蛋白重链和CD3δ增强子中有脱氧核糖核酸酶I超敏位点,并转录种系T细胞抗原受体γ链(TCRγ)基因,但不转录IgM或TCRβ基因。这些细胞中髓系分化的诱导会克隆性下调免疫球蛋白重链和TCRγ基因的表达和/或转录可及性。CD3δ增强子区域仍然对脱氧核糖核酸酶I敏感,但在B细胞中关闭。在胚胎干细胞和全中胚层细胞中,这些基因或增强子区域既不表达也不对脱氧核糖核酸酶I敏感。这些数据表明,谱系潜能可能至少部分地由基因调控区域的可及性或构象改变所编程,并且在由白细胞介素3诱导自我更新的祖细胞中,在谱系定型和成熟之前可能存在一些基因表达和/或可及性的混杂情况。