Thursday, January 21, 2010


MAML1 Enhances the Transcriptional Activity of Runx2 and Plays a Role in Bone Development.

"Mastermind-like 1 (MAML1) is a transcriptional co-activator in the Notch signaling pathway. MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2), a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2) from the Runx2-regulated osteocalcin gene promoter. A deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Inhibition of Notch signaling did not affect the action of MAML1 on Runx2, [thus] activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/-) embryos at embryonic day 16.5 (E16.5) had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1) and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1) expression, a marker of hypertrophic chondrocyte, were observed{but we can't know if this results in an increase or decrease of adult height}. Chondrocyte maturation was impaired in MAML1(-/-) mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development."

MAML2 also enhances RUNX2 transcriptional activity.

" the expression of Sox9, a transcription activator of collagen type II, was upregulated by Notch activation and this activation of Notch signaling thereby promoted differentiation of proliferative and prehypertrophic chondrocytes"

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