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question 36

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Use the following information when answering the corresponding questions) .
A group of enzymes known as cytosine- specific DNA methylases recognize CpG dinucleotide sequences-that is, a cytosine followed by a guanosine G) in one DNA strand-and add methyl groups to the cytosine. Many proteins bind to methylated CpG, including the methyl- CpG binding protein 2 MeCP2) . MeCP2 binding leads to the formation of a closed state of chromatin, thus silencing gene expression. A recent paper by Chen et al. reported an interesting mechanism of regulating transcription of a gene via MeCP2 W. Chen, Q. Chang, Y. Lin, A. Meissner, A. E. West, E. C. Griffith, R. Jaenish, and M. Greenberg. 2004. Derepression of BDNF transcription involves calcium- dependent phosphorylation of MeCP2, Science 302:885-89) . This gene, called BDNF, encodes brain- derived neurotrophic factor BDNF) -a protein that plays an important role in nerve cell and central nervous system function, including memory and learning. Remarkably, most cases of Rett syndrome, an important cause of mental retardation in females, are due to loss- of- function mutations of MeCP2.
-The authors state, "In this study, we report that, in the absence of neuronal activity, MeCP2 binds specifically to BDNF promoter III and functions as a negative regulator of BDNF expression. In response to neuronal Activity- dependent calcium influx into neurons, MeCP2 becomes phosphorylated and is released from the BDNF promoter, thereby permitting BDNF promoter III- dependent transcription." Reading this statement in isolation, it would be easy to have the impression that MeCP2 works as a negatively acting transcription factor. However, based on the summary of the paper provided above, MeCP2 acts as a


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