Control of Embryonic hunchback Gene Expression by Maternal bicoid Protein in Drosophila (p. 415/416)
Gene Activation by Histone Acetylation in Yeast (p. 421/422)
Drosophila Homeotic Gene Activity (p. 423-425)
p. 409, Fig. 16.4: The core promoter region upstream of the TATA box should be bound by TFIIB rather than TFIIA. See review article by Butler and Kadonaga (2002), Fig.1 for update.
Brivanlou AH and Darnell JE Jr. (2002) Signal transduction and the control of gene expression. Science 295: 813-818
Butler J.E.F. and Kadonaga J.T. (220) The RNA polymerase II core promoter: a key component in the regulation of gene expression. Genes & Devel. 16: 2583-2592
Courey AJ and Jia S. (2001) Transcriptional repression: the long and the short of it. Genes Dev. 15: 2786-2796.
Emerson B.M. (2002) Specificity of gene regulation. Cell 109: 267-270
Hochheimer A. and Tijan R. (2003) Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression. Genes & Devel. 17: 1309-1320
Jones P.A. and Takai D. (2001) The role of DNA methylation in mammalian epigenetics. Science 293: 1068-1070
Lemon B. and Tijan R. (2000) Orchestrated response: a symphony of transcription factors for gene control. Genes & Devel. 14: 2552-2569
Maniatis T and Reed R. (2002) An extensive network of coupling among gene expression machines. Nature 416: 499-506
Orlando V. (2003) Polycomb, epigenomes, and control of cell identity. Cell 112: 599-606
Orphanides G and Reinberg D. (2002) A unified theory of gene expression. Cell 108: 439-451
West AG, Gaszner M and Felsenfeld G. (2002) Insulators: many functions, many mechanisms. Genes Dev. 16: 271-288
Zhang Y. and Reinberg D. (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes & Devel. 15: 2343-2360
Bell A.C. and Felsenfeld G. (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405: 482-485
Hark A.T., Schoenherr C.J., Katz D.J., Ingram R.S., Levorce J.M. and Tilghman S.M. (2000) CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405: 486-489
Srivastava M., Hsieh S., Grinberg A., Williams-Simons L., Huang S.P. and Pfeifer K. (2000) H19and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis-acting regulatory region upstream of H19. Genes & Devel. 14: 1186-1195
These three studies show that DNA methylation may control gene expression by modulating the binding site for a boundary protein. The H19 and Igf2 genes in mice share an enhancer region located downstream of both genes and close to H19. The two genes are oppositely imprinted: On the maternal chromosome, H19 uses the enhancer and is expressed whereas Igf2 is silent. On the paternal chromosome, Igf2 uses the enhancer and is expressed whereas H19 is silent. The three papers describe a imprinting-control region (ICR), which is located between Igf2 and H19, but closer to H19. ICR is controlled by methylation. In the unmethylated state, ICR is bound by CTCF, a "boundary" protein preventing the interaction between enhancers and promoters. On the maternal chromosome, ICR is unmethylated, allowing CTCF to bind and to prevent the enhancer from interacting with Igf2, which is not expressed. However, the enhancer can interact with H19, which is also unmethylated, so that H19 is expressed. On the paternal chromosome, ICR is methylated so that CTCF does not bind. Since the H19 promoter is also methylated this gene is not expressed. However, in the absence of the CTCF boundary, the enhancer can interact with Igf2, so that this gene is expressed.
Evolutionary Explanation of Imprinting
Haig D. and Westoby M. (2006) An earlier formulation of the genetic conflict hypothesis of genomic imprinting. Nature Genet. 38: 271.
The sex-specific and reversible silencing of certain autosomal genes in mammals is known as genomic imprinting
Some genes (about 30-40) are imprinted during spermatogenesis while others are imprinted during oogenesis.
The imprinted genes remain silent in early embryonic and in all somatic cells, including the brain. The homologous genes are then expressed uniparentally.
The imprinting is erased is erased in the primordial germ cells of each new generation, so that germ line cells express both alleles of previously imprinted genes.
During gametogenesis, each parent again imprints the sex-specific set of genes.
The ultimate cause of imprinting seems to be a conflict over the amount of maternal nutrients diverted to her offspring via placental circulation or nursing. Fathers seem to imprint genes that would otherwise limit the amount of maternal nutrients received by the offspring, whereas mothers imprint genes that would otherwise have the opposite effect.
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