1.In eukaryotes, DNA methylation is involved in all the following except: a.regu
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Question
1.In eukaryotes, DNA methylation is involved in all the following except:
a.regulating transcription by methylation at CpG island
b.enhancing compacted conformation of DNA
c.genomic imprinting of genes that come from either parent
d.methyl-directed mismatch repair
e.all of the above are involved
2. The enzyme histone acetyltransferase is directly involved in which of the following?
a.removal of histones from chromatin
b.movement of nucleosomes
c.chemical modification of histones
d.termination of gene expression
e.insertion of variant histone proteins
Explanation / Answer
1. DNA methylation is the only covalent modification of DNA and involves transfer of methyl group from S- adenosyl methionin to C5 positon of pyrimidine ring of cytosine to form 5-methylcytosine (5mC). The process is reversible and is independent on the sequence, hence it is an epigenetic mechanism of gene regulation. This mechanism regulates gene expression by recruiting proteins for gene repression or preventing transcription factor(s) from binding to DNA. Commonly the process occurs on cytosines preceding guanine or CpG sites. In mammalian genomes CpG sites are mostly depleted due to deamination of 5mC to thymine. The remaining CpG sites are separated and heavily methylated except at CpG islands. The CpG sites or islands are rarely methylated due to the bound transcription factors that block DNA MTase. The methylated sequences are usually inactive.
DNA methylation is essential for silencing retroviral elements. The inserted viral sequences are methylated, and silenced in humans and mice. DNA methylation also regulates tissue-specific gene expression, genomic imprinting, and X chromosome inactivation. The different genomic regions exert different influences on gene activities based on the underlying genetic sequence.
DNA methylation induces compact and rigid nucleosome structure, and regulates the chromatin structure. In eukaryotic cells, DNA is arranged into nucleosomes, by wrapping ~147bp of DNA by histone octamer and folding into higher order chromatin structures. Methylation of the CpG dinucleotides is one epigenetic modification to this structure.
Genomic imprinting is an epigenetic phenomenon occurring during the gametogenesis. It occurs when both maternal and paternal alleles are present, but only one allele is expressed and the other is inactive. DNA methylation by the enzyme DNA methyltransferase (DNA MTase) is the optimal method for gene imprinting in mammals. The enzyme acts on the DNA sequence 5'-CpG-3'.
2. HAT serves many biological roles inside the cell. They regulate epigenetic gene expression and chromatin remodeling. They neutralize charged lysine residues, allowing the chromatin to decondense and making them accessible to gene transcription. They also act as transcriptional co-activators or gene silencers and often found in large complexes of 10 to 20 subunits, some even shared among different HAT complexes. They catalyze the transfer an acetyl group from acetyl-CoA to specific lysine residues on histones, which neutralizes their positive charge and thus reduces the strong interactions between the histone and DNA. They also serve as binding site for chromatin complexes.The ability of histone acetyltransferases to manipulate chromatin structure makes them assist in the reformation of nucleosomes and repair of damaged DNA.
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