Diekwisch Lab: Epigenetics & Chromatin

Two decades ago, we cloned and sequenced the SRCAP chromatin complex member cp27 in our laboratory (Diekwisch et al. 1999). This factor turned out to have essential roles in embryonic development and cell division (Diekwisch and Luan 2002, Luan and Diekwisch 2002). We then characterized the cp27 promoter and identified the CCAAT box binding transcription factor NF-Y as one of its key regulators (Luan et al. 2010, Ito et al. 2011). Currently, we are defining the role of this factor in chromatin segregation and craniofacial syndromes. The essential function of chromatin in early development prompted us to ask how epigenetic factors contribute to the differentiation of dental tissues. Here we focused on histone modifications as early marks in tissue differentiation. Our studies identified a switch from active to repressive histone marks during periodontal differentiation (Dangaria et al. 2011). We also reported that dentin-related genes such as DSPP and DMP are repressed in dental follicle progenitors while they are active in dental pulp lineage (Gopinathan et al. 2013).

 

CP27 localization in a fibroblast nucleus. 20 years ago we have discovered the CP27 gene in our laboratory. Today, the gene is called CFDP1 (craniofacial development protein 1). As a chromatin complex member, it plays an important role in the regulation of transcription.

 

Contributions to Journals

Gopinathan G., Kolokythas, A., Luan, X., and Diekwisch, T.G.H. (2013). Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived odontogenic progenitors. Stem Cells Dev. 22, 1763-1778.

Dangaria, S., Ito, Y., Luan, X., and Diekwisch, T.G.H. (2011). Differentiation of neural crest-derived intermediate pluripotent progenitors into committed periodontal population involves unique molecular signature changes, cohort shifts, and epigenetic modifications. Stem Cells and Development 20, 39-52.

Ito, Y., Zhang, Y., Dangaria, S., Luan, X., and Diekwisch, T.G.H. (2011). NF-Y and USF1 transcription factor binding to CCAAT box and E-box elements activates the CP27 promoter. Gene 473, 92-99.

Luan, X., Ito, Y., Zhang, Y., and Diekwisch, T.G.H. (2010). Characterization of the mouse CP27 promoter and NF-Y mediated gene regulation. Gene 460, 8-19.

Diekwisch, T.G.H., Luan, X., and McIntosh, J.E. (2002). CP27 localization in the dental lamina basement membrane and in the stellate reticulum of developing teeth. J. Histochem. Cytochem 50, 583-585.

Luan, X., and Diekwisch, T.G.H. (2002). CP27 affects viability, proliferation, attachment, and gene expression in embryonic fibroblasts. Cell Proliferation 35, 207-219.

Diekwisch, T.G.H. and Luan, X. (2002). CP27 function is necessary for cell survival and differentiation during tooth morphogenesis in organ culture. Gene 287, 141-147.

Diekwisch, T.G.H., Marches, F., Williams, A., and Luan, X. (1999). Cloning, gene expression, and characterization of CP27, a novel gene in mouse embryogenesis. Gene 235, 19-30.

 

Epigenetic regulation of dentin-related genes in neural crest progenitors. Dental follicle and dental papilla are neural crest derived odontogenic progenitors giving rise to periodontal tissues (dental follicle) and the dentin-pulp complex (dental papilla). Dentin-related genes such as DMP1 and DSPP display remarkably high levels of repression in dental follicle progenitors, as evidenced by ChIP-chip promoter enrichment profiles (Gopinathan et al. 2013, Stem Cells and Development). These data demonstrate the significant role of histone lysine methylation in progenitor fate determination.