TY - JOUR
T1 - Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development
AU - Tsuji-Takechi, Kaori
AU - Negishi-Koga, Takako
AU - Sumiyaa, Eriko
AU - Kukita, Akiko
AU - Kato, Shigeaki
AU - Maeda, Takahiro
AU - Pandolfi, Pier Paolo
AU - Moriyama, Keiji
AU - Takayanagi, Hiroshi
PY - 2012/2/14
Y1 - 2012/2/14
N2 - Cell fate determination is tightly regulated by transcriptional activators and repressors. Leukemia/lymphoma-related factor (LRF; encoded by Zbtb7a), known as a POK (POZ/BTB and Krüppel) family transcriptional repressor, is induced during the development of bone-resorbing osteoclasts, but the physiological significance of LRF in bone metabolism and the molecular mechanisms underlying the transcriptional regulation of osteoclastogenesis by LRF have not been elucidated. Herewe show that LRF negatively regulates osteoclast differentiation by repressing nuclear factor of activated T cells c1 (NFATc1) induction in the early phase of osteoclast development, while positively regulating osteoclast-specific genes by functioning as a coactivator of NFATc1 in the bone resorption phase. The stage-specific distinct functions of LRF were demonstrated in two lines of conditional knockout mice in which LRF was deleted in the early or late phase of osteoclast development. Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment.
AB - Cell fate determination is tightly regulated by transcriptional activators and repressors. Leukemia/lymphoma-related factor (LRF; encoded by Zbtb7a), known as a POK (POZ/BTB and Krüppel) family transcriptional repressor, is induced during the development of bone-resorbing osteoclasts, but the physiological significance of LRF in bone metabolism and the molecular mechanisms underlying the transcriptional regulation of osteoclastogenesis by LRF have not been elucidated. Herewe show that LRF negatively regulates osteoclast differentiation by repressing nuclear factor of activated T cells c1 (NFATc1) induction in the early phase of osteoclast development, while positively regulating osteoclast-specific genes by functioning as a coactivator of NFATc1 in the bone resorption phase. The stage-specific distinct functions of LRF were demonstrated in two lines of conditional knockout mice in which LRF was deleted in the early or late phase of osteoclast development. Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment.
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U2 - 10.1073/pnas.1116042109
DO - 10.1073/pnas.1116042109
M3 - Article
C2 - 22308398
AN - SCOPUS:84857130450
SN - 0027-8424
VL - 109
SP - 2561
EP - 2566
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -