Change in nuclear-cytoplasmic localization of a double-bromodomain protein during proliferation and differentiation of mouse spinal cord and dorsal root ganglia

The human Brd2 (Bromodomain-containing 2) gene codes for a double-bromodomain protein that associates with the cell cycle-driving transcription factors E2F-1 and E2F-2. Expression of mouse Brd2 has been shown previously to be expressed in specific patterns in proliferating cells in the developing alveoli in the mammary gland. In the present study, in situ hybridization and immunohistochemical analyses were used to examine expression of Brd2 in developing neural tissues. Brd2 mRNA was detected in brain vesicles, neural tube, spinal cord and dorsal root ganglia (DRG). Immunostaining proved that the message is translated in these tissues and further revealed that Brd2 protein localizes to the nucleus in proliferating cells, but is cytoplasmic in differentiated neurons that are no longer cycling. Brd2 protein in the nuclei of the proliferating neuronal precursors is excluded from the heterochromatin. These observations are consistent with our previous finding that nuclear localization of Brd2 protein correlates with an active cell cycle in mouse mammary alveoli during the reproductive cycle, and similar results from others in cultured fibroblasts. Our findings are also consistent with the cell cycle progression/transcription coactivator function suggested by the association of Brd2 with E2F-1 and E2F-2.