The transcription factor early B-cell factor 1 regulates bone formation in an osteoblast-nonautonomous manner

Early B-cell factor 1 (Ebf1) is a transcription factor whose inactivation in all cells results in high bone mass because of an increase in bone formation. This observation suggests Ebf1 may be an inhibitor of osteoblast differentiation. To test this contention, we analyzed Ebf1 pattern of expression and function in osteoblasts ex vivo and in vivo through osteoblast-specific inactivation in the mouse. We show here that in vivo deletion of Ebf1 in osteoblast progenitors does not affect osteoblast differentiation or bone formation accrual post-natally. These observations indicate that the phenotype described in Ebf1-/- mice is not osteoblast-autonomous

Human mutations affect the epigenetic/bookmarking function of HNF1B

International audienceBookmarking factors are transcriptional regulators involved in the mitotic transmission of epigenetic information via their ability to remain associated with mitotic chromatin. The mechanisms through which bookmarking factors bind to mitotic chromatin remain poorly understood. HNF1␤ is a bookmarking transcription factor that is frequently mutated in patients suffering from renal multicystic dysplasia and diabetes. Here, we show that HNF1␤ bookmark-ing activity is impaired by naturally occurring mutations found in patients. Interestingly, this defect in HNF1␤ mitotic chromatin association is rescued by an abrupt decrease in temperature. The rapid re-localization to mitotic chromatin is reversible and driven by a specific switch in DNA-binding ability of HNF1␤ mutants. Furthermore, we demonstrate that importin-␤ is involved in the maintenance of the mi-totic retention of HNF1␤, suggesting a functional link between the nuclear import system and the mi-totic localization/translocation of bookmarking factors. Altogether, our studies have disclosed novel aspects on the mechanisms and the genetic programs that account for the mitotic association of HNF1␤, a bookmarking factor that plays crucial roles in the epigenetic transmission of information through the cell cycle