Department of Cell and Developmental Biology
Activating Transcription Factor 4; Animals; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Histone Deacetylases; MEF2 Transcription Factors; Mice; Models, Biological; Osteoblasts; Parathyroid Hormone; RANK Ligand; *Signal Transduction; Ubiquitin-Protein Ligases; Ubiquitination
Parathyroid hormone (PTH) and the sympathetic tone promote Rankl expression in osteoblasts and osteoclast differentiation by enhancing cyclic adenosine monophosphate production through an unidentified transcription factor for PTH and through ATF4 for the sympathetic tone. How two extracellular cues using the same second messenger in the same cell elicit different transcriptional events is unknown. In this paper, we show that PTH favors Rankl expression by triggering the ubiquitination of HDAC4, a class II histone deacetylase, via Smurf2. HDAC4 degradation releases MEF2c, which transactivates the Rankl promoter. Conversely, sympathetic signaling in osteoblasts favors the accumulation of HDAC4 in the nucleus and its association with ATF4. In this context, HDAC4 increases Rankl expression. Because of its ability to differentially connect two extracellular cues to the genome of osteoblasts, HDAC4 is a critical regulator of osteoclast differentiation.
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Citation: J Cell Biol. 2014 Jun 23;205(6):771-80. doi: 10.1083/jcb.201403138. Link to article on publisher's site. Epub 2014 Jun 16.
The Journal of cell biology
Obri, Arnaud; Makinistoglu, Munevver Parla.; Zhang, Hong; and Karsenty, Gerard, "HDAC4 integrates PTH and sympathetic signaling in osteoblasts" (2014). Cell and Developmental Biology Publications and Presentations. Paper 151.
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