The role of the polycomb complex in silencing alpha-globin gene expression in nonerythroid cells. Export

@article{citeulike:6086911, abstract = {Although much is known about globin gene activation in erythroid cells, relatively little is known about how these genes are silenced in nonerythroid tissues. Here we show that the human alpha- and beta-globin genes are silenced by fundamentally different mechanisms. The alpha-genes, which are surrounded by widely expressed genes in a gene dense region of the genome, are silenced very early in development via recruitment of the Polycomb (PcG) complex. By contrast, the beta-globin genes, which lie in a relatively gene-poor chromosomal region, are not bound by this complex in nonerythroid cells. The PcG complex seems to be recruited to the alpha-cluster by sequences within the CpG islands associated with their promoters; the beta-globin promoters do not lie within such islands. Chromatin associated with the alpha-globin cluster is modified by histone methylation (H3K27me3), and silencing in vivo is mediated by the localized activity of histone deacetylases (HDACs). The repressive (PcG/HDAC) machinery is removed as hematopoietic progenitors differentiate to form erythroid cells. The alpha- and beta-globin genes thus illustrate important, contrasting mechanisms by which cell-specific hematopoietic genes (and tissue-specific genes in general) may be silenced.}, author = {Garrick, David and De Gobbi, Marco and Samara, Vasiliki and Rugless, Michelle and Holland, Michelle and Ayyub, Helena and Lower, Karen and Sloane-Stanley, Jackie and Gray, Nicki and Koch, Christoph and Dunham, Ian and Higgs, Douglas R.}, citeulike-article-id = {6086911}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2008-06-161901}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18689541}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18689541}, day = {1}, doi = {10.1182/blood-2008-06-161901}, issn = {1528-0020}, journal = {Blood}, keywords = {d-polycomb}, month = {November}, number = {9}, pages = {3889--3899}, posted-at = {2009-11-09 02:33:08}, priority = {2}, title = {The role of the polycomb complex in silencing alpha-globin gene expression in nonerythroid cells.}, url = {http://dx.doi.org/10.1182/blood-2008-06-161901}, volume = {112}, year = {2008} }

TY - JOUR ID - citeulike:6086911 L3 - citeulike-article-id:6086911 N2 - Although much is known about globin gene activation in erythroid cells, relatively little is known about how these genes are silenced in nonerythroid tissues. Here we show that the human alpha- and beta-globin genes are silenced by fundamentally different mechanisms. The alpha-genes, which are surrounded by widely expressed genes in a gene dense region of the genome, are silenced very early in development via recruitment of the Polycomb (PcG) complex. By contrast, the beta-globin genes, which lie in a relatively gene-poor chromosomal region, are not bound by this complex in nonerythroid cells. The PcG complex seems to be recruited to the alpha-cluster by sequences within the CpG islands associated with their promoters; the beta-globin promoters do not lie within such islands. Chromatin associated with the alpha-globin cluster is modified by histone methylation (H3K27me3), and silencing in vivo is mediated by the localized activity of histone deacetylases (HDACs). The repressive (PcG/HDAC) machinery is removed as hematopoietic progenitors differentiate to form erythroid cells. The alpha- and beta-globin genes thus illustrate important, contrasting mechanisms by which cell-specific hematopoietic genes (and tissue-specific genes in general) may be silenced. IS - 9 JF - Blood SN - 1528-0020 EP - 3899 TI - The role of the polycomb complex in silencing alpha-globin gene expression in nonerythroid cells. VL - 112 SP - 3889 KW - d-polycomb AU - Garrick, David AU - De Gobbi, Marco AU - Samara, Vasiliki AU - Rugless, Michelle AU - Holland, Michelle AU - Ayyub, Helena AU - Lower, Karen AU - Sloane-Stanley, Jackie AU - Gray, Nicki AU - Koch, Christoph AU - Dunham, Ian AU - Higgs, Douglas PY - 2008/11/01/ UR - http://dx.doi.org/10.1182/blood-2008-06-161901 ER -