description): Homeobox (Hox) genes are essential determinants of axial patterning during embryonic development of a wide variety of organisms ranging from the fruitfly to man. In all species studied to date, the Hox genes are closely linked on the chromosome in clusters of about 5-11 genes. Once genes in the clusters are expressed, their expression pattern is maintained by the activity of the Polycomb (PcG) and trithorax (trxG) group proteins. PcG proteins maintain Hox genes in an off state, while trxG proteins maintain expression in an on state through multiple cell divisions. This proposal aims to identify mechanisms involved in this epigenetic control of Hox gene expression by PcG and trxG proteins. Both protein groups presumably work by affecting accessibility of the chromatin to transcription factors by an unknown mechanism. This study aims to first, determine the histone acetylation state of the mammalian clusters. Second, the investigators will map the interaction of PcG and trxG proteins across the Hoxb cluster and correlate these interactions with histone acetylation. As a model system, the investigators will use the embryonal carcinoma cell line, P19, which can be induced with retinoic acid to activate Hox gene expression leading to neuronal cell types.
