Lijuan Zhao
Harvard University
Molecular biologyRecombination signal sequencesLeukemiaMyeloid leukemiaBiology
What is this?
Publications 7
#1Liang Chen (Duke University)H-Index: 7
#2Lijuan Zhao (Harvard University)H-Index: 5
Last. Michael S. Krangel (Duke University)H-Index: 54
view all 4 authors...
Chromatin looping mediated by the CCCTC binding factor (CTCF) regulates V(D)J recombination at Ag receptor loci. CTCF-mediated looping can influence recombination signal sequence (RSS) accessibility by regulating enhancer activation of germline promoters. CTCF-mediated looping has also been shown to limit directional tracking of the RAG recombinase along chromatin, and to regulate long-distance interactions between RSSs, independent of the RAG recombinase. However, in all prior instances in whic...
5 CitationsSource
#1Lijuan Zhao (HHMI: Howard Hughes Medical Institute)H-Index: 5
#2Richard L. Frock (HHMI: Howard Hughes Medical Institute)H-Index: 14
Last. Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
view all 7 authors...
T cell antigen receptor δ ( Tcrd ) variable region exons are assembled by RAG-initiated V(D)J recombination events in developing γδ thymocytes. Here, we use linear amplification–mediated high-throughput genome-wide translocation sequencing (LAM-HTGTS) to map hundreds of thousands of RAG-initiated Tcrd D segment ( Trdd1 and Trdd2 ) rearrangements in CD4−CD8− double-negative thymocyte progenitors differentiated in vitro from bone marrow–derived hematopoietic stem cells. We find that Trdd2 joins di...
17 CitationsSource
#1Jiazhi Hu (Boston Children's Hospital)
#2Yu Zhang (Boston Children's Hospital)
Last. Frederick W. Alt (Boston Children's Hospital)H-Index: 157
view all 9 authors...
Recombination activating gene 1/2 endonuclease (RAG) initiates V(D)J recombination in developing B and T lymphocytes via “on-target” activity at bona fide recombination signal sequences (RSSs) to generate diverse antibodies. “Off-target” RAG activity is thought to be rare, but can cause oncogenic interstitial deletions or chromosomal translocations that contribute to immature B and T lymphocyte cancers. Given that potential RAG off-target sites occur frequently in the genome, it has been a myste...
#1Jiazhi Hu (Harvard University)H-Index: 12
#2Yu Zhang (Harvard University)H-Index: 45
Last. Frederick W. Alt (Harvard University)H-Index: 157
view all 9 authors...
Summary RAG initiates antibody V(D)J recombination in developing lymphocytes by generating "on-target" DNA breaks at matched pairs of bona fide recombination signal sequences (RSSs). We employ bait RAG-generated breaks in endogenous or ectopically inserted RSS pairs to identify huge numbers of RAG "off-target" breaks. Such breaks occur at the simple CAC motif that defines the RSS cleavage site and are largely confined within convergent CTCF-binding element (CBE)-flanked loop domains containing b...
68 CitationsSource
#1Lijuan Zhao (SJTU: Shanghai Jiao Tong University)H-Index: 5
#2Yue-Ying Wang (SJTU: Shanghai Jiao Tong University)H-Index: 11
Last. Shenjian Chen (SJTU: Shanghai Jiao Tong University)H-Index: 82
view all 10 authors...
The BCR-ABL fusion protein generated by t(9;22)(q34;q11) in chronic myeloid leukemia (CML) plays an essential role in the pathogenesis of the myeloproliferative disorder status at the chronic phase of the disease, but progression from the chronic phase to blast crisis (BC) is believed to require additional mutations. To explore the underlying mechanisms for BC, which is characterized by a blockage of blood cell differentiation, we screened several genes crucial to hematopoiesis and identified 10...
25 CitationsSource
#1Bo WuH-Index: 1
#2Zhu ChenH-Index: 70
Last. Wei-Na ZhangH-Index: 8
view all 10 authors...
The full-length AML1-ETO (AE) fusion gene resulting from t(8;21)(q22;q22) in human acute myeloid leukemia (AML) is not sufficient to induce leukemia in animals, suggesting that additional mutations are required for leukemogenesis. We and others have identified activating mutations of C-KIT in nearly half of patients with t(8;21) AML. To test the hypothesis that activating C-KIT mutations cooperate with AE to cause overt AML, we generated a murine transduction and transplantation model with both ...
86 CitationsSource