Role of topoisomerase IIbeta in the expression of developmentally regulated genes. Export

@article{citeulike:1251831, abstract = {Mice lacking topoisomerase IIbeta (TopIIbeta) are known to exhibit a perinatal death phenotype. In the current study, transcription profiles of the brains of wild-type and top2beta knockout mouse embryos were generated. Surprisingly, only a small number (1 to 4\%) of genes were affected in top2beta knockout embryos. However, the expression of nearly 30\% of developmentally regulated genes was either up- or down-regulated. By contrast, the expression of genes encoding general cell growth functions and early differentiation markers was not affected, suggesting that TopIIbeta is not required for early differentiation programming but is specifically required for the expression of developmentally regulated genes at later stages of differentiation. Consistent with this notion, immunohistochemical analysis of brain sections showed that TopIIbeta and histone deacetylase 2, a known TopIIbeta-interacting protein, were preferentially expressed in neurons which are in their later stages of differentiation. Chromatin immunoprecipitation analysis of the developing brains revealed TopIIbeta binding to the 5' region of a number of TopIIbeta-sensitive genes. Further studies of a TopIIbeta-sensitive gene, Kcnd2, revealed the presence of TopIIbeta in the transcription unit with major binding near the promoter region. Together, these results support a role of TopIIbeta in activation/repression of developmentally regulated genes at late stages of neuronal differentiation.}, address = {Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.}, author = {Lyu, Y. L. and Lin, C. P. and Azarova, A. M. and Cai, L. and Wang, J. C. and Liu, L. F.}, citeulike-article-id = {1251831}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/MCB.00617-06}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16923961}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16923961}, doi = {10.1128/MCB.00617-06}, issn = {0270-7306}, journal = {Mol Cell Biol}, keywords = {development, gene\_expression, mouse, topoisomerase, topoisomerase\_iibeta}, month = {November}, number = {21}, pages = {7929--7941}, posted-at = {2007-04-26 05:05:48}, priority = {3}, title = {Role of topoisomerase IIbeta in the expression of developmentally regulated genes.}, url = {http://dx.doi.org/10.1128/MCB.00617-06}, volume = {26}, year = {2006} }

TY - JOUR ID - citeulike:1251831 L3 - citeulike-article-id:1251831 N2 - Mice lacking topoisomerase IIbeta (TopIIbeta) are known to exhibit a perinatal death phenotype. In the current study, transcription profiles of the brains of wild-type and top2beta knockout mouse embryos were generated. Surprisingly, only a small number (1 to 4%) of genes were affected in top2beta knockout embryos. However, the expression of nearly 30% of developmentally regulated genes was either up- or down-regulated. By contrast, the expression of genes encoding general cell growth functions and early differentiation markers was not affected, suggesting that TopIIbeta is not required for early differentiation programming but is specifically required for the expression of developmentally regulated genes at later stages of differentiation. Consistent with this notion, immunohistochemical analysis of brain sections showed that TopIIbeta and histone deacetylase 2, a known TopIIbeta-interacting protein, were preferentially expressed in neurons which are in their later stages of differentiation. Chromatin immunoprecipitation analysis of the developing brains revealed TopIIbeta binding to the 5' region of a number of TopIIbeta-sensitive genes. Further studies of a TopIIbeta-sensitive gene, Kcnd2, revealed the presence of TopIIbeta in the transcription unit with major binding near the promoter region. Together, these results support a role of TopIIbeta in activation/repression of developmentally regulated genes at late stages of neuronal differentiation. IS - 21 JF - Mol Cell Biol SN - 0270-7306 AD - Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. EP - 7941 TI - Role of topoisomerase IIbeta in the expression of developmentally regulated genes. VL - 26 SP - 7929 KW - development KW - gene_expression KW - mouse KW - topoisomerase KW - topoisomerase_iibeta AU - Lyu, YL AU - Lin, CP AU - Azarova, AM AU - Cai, L AU - Wang, JC AU - Liu, LF PY - 2006/11// UR - http://dx.doi.org/10.1128/MCB.00617-06 ER -