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Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development
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Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development
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Journal Article
Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development
2012
Overview
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. Here we 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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Bones
/ Cells
/ DNA-Binding Proteins - physiology
/ Genes
/ Humans
/ Leukemia
/ Lymphoma
/ Mice
/ Proteins
