PRDM family members are transcriptional regulators involved in tissue specific differentiation. PRDM5 has been reported to predominantly repress transcription, but a characterization of its molecular functions in a relevant biological context is lacking.
Bone is composed of a highly specialized, mineralized collagenous matrix that provides tensile strength to the skeletal system. Collagen I is the major component of osteoblasts matrix. Approximately 40 collagen genes are annotated in mammalian genomes encoding around 28 proteins. A number of transcription factors have been discovered as regulators of collagen I genes, such as Sp1, Cebpbß or members of the AP1 family. Furthermore, a number of transcription factors are known to be key regulators of bone development, such as Runx2, which controls the expression of a multitude of extracellular matrix (ECM) genes essential for both the chondrogenic and osteogenic programs.
In the study of Galli et al. a novel role of Prdm5 is presented. In collaboration with the German Mouse Clinic it was identified that the process of ossification is delayed in mutant mice. Additionally, assembly of fibrillar collagens is strongly impaired. As a consequence bone mineral density is reduced in mutant animals.
The scientists showed for the first time, that the transcription factor Prdm5 is strongly expressed during bone development and that it regulates the transcription of collagen 1 as well as the fibrillogenesis.
Giorgio Giacomo Galli et al., Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone. PLoS Genet. 2012 May; 8(5): e1002711.