In the post-genomic era, a great deal of work has focused on understanding how DNA sequence is used to programme complex nuclear, cellular and tissue functions throughout differentiation and development. There are many approaches to these issues, but we have concentrated on understanding how a single mammalian gene cluster is activated or silenced as stem cells undergo lineage commitment, differentiation and maturation. In particular we have analysed the α globin cluster, which is expressed in a cell-type- and developmental stage-specific manner in the haemopoietic system. Our studies include analysis of the transcriptional programme that accompanies globin gene activation, focusing on the expression of relevant transcription factors and cofactors. Binding of these factors to the chromosomal domain containing the α globin cluster has been characterized by ChIP (chromatin immunoprecipitation). In addition, we have monitored the epigenetic modifications (e.g. nuclear position, timing of replication, chromatin modification, DNA methylation) that occur as the genes are activated (in erythroid cells) or silenced (e.g. in granulocytes) as haemopoiesis proceeds. Together, these observations provide a uniquely well-characterized model illustrating the mechanisms that regulate and memorize patterns of mammalian gene expression as stem cells undergo lineage specification, differentiation and terminal maturation.
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January 2006
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Conference Article|
January 01 2006
How transcriptional and epigenetic programmes are played out on an individual mammalian gene cluster during lineage commitment and differentiation
Douglas R. Higgs;
Douglas R. Higgs
1
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
1To whom correspondence should be addressed (email [email protected]).
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Douglas Vernimmen;
Douglas Vernimmen
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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Marco De Gobbi;
Marco De Gobbi
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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Eduardo Anguita;
Eduardo Anguita
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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Jim Hughes;
Jim Hughes
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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Veronica Buckle;
Veronica Buckle
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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Franciso Iborra;
Franciso Iborra
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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David Garrick;
David Garrick
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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William G. Wood
William G. Wood
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2006 Biochemical Society
2006
Biochem Soc Symp (2006) 73: 11–22.
Citation
Stefan G.E. Roberts, Robert O.J. Weinzierl, Robert J. White, Douglas R. Higgs, Douglas Vernimmen, Marco De Gobbi, Eduardo Anguita, Jim Hughes, Veronica Buckle, Franciso Iborra, David Garrick, William G. Wood; How transcriptional and epigenetic programmes are played out on an individual mammalian gene cluster during lineage commitment and differentiation. Biochem Soc Symp 1 January 2006; 73 11–22. doi: https://doi.org/10.1042/bss0730011
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