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so the regulation of gene expression can be modulated of virtually any step in the process from the initiation of transcription all the way to post translational modification with protein and every step in between and it's the ability to regulate all these different steps that helps the cell to have the versatility and the adaptability of an efficient ninja so that it expends energy to express the appropriate proteins only when needed or you can think of the cell as a lazy couch potato that wants to expend the least amount of energy as possible so starting at the beginning of gene expression let's talk about gene regulation as it pertains to DNA and chromatin regulation let's talk about the structure of DNA DNA is packed into chromosomes in the form of chromatin also known as super coiled DNA and so chromatin is made up of DNA histone proteins and non-histone proteins and there are repeating units in chromatin called nucleosomes which are made up of 146 base pairs of double helical DNA that is wrapped around a core of eight histones and there are four different types of histones within this structure of eight that you should be aware of and they're named h-2a h-2b h3 and h4 that's just the nomenclature they've been given now acetylation occurs at the amino terminal tails of these histone proteins by an enzyme called histone acetyl transferase which I'll just abbreviate as hae and this is a reversible modification so the acetylation of histones is sort of kept in balance by another enzyme that removes these acetyl groups which is called histone deacetylase or HD ACH DAC the acetylation of histones leads to uncoiling of this chromatin structure and this allows it to be accessed by transcriptional machinery for the expression of genes on the flip side of this histone deacetylation leads to a condensed or closed structure of the chromatin and less transcription of those genes when these modifications that regulate gene expression are inheritable they are referred to as epigenetic regulation so when it comes to gene expression and DNA you can basically think of DNA as coming in two flavors densely packed and transcriptionally inactive DNA which is called heterochromatin and then less dense transcriptionally active DNA which is euchromatin and I like to think of heterochromatin as as being densely packed and hibernating like heterochromatin and hibernating both begin with H kind of like a bunch of densely packed bears that are closed off in there k for the winter whereas euchromatin is waiting there with open arms welcoming the transcriptional machinery to transcribe away now often you will see that histone deacetylation is combined with another type of DNA regulatory mechanism and that is DNA methylation and this occurs in a process called gene silencing and this is a more permanent method of sort of down regulating the transcription of genes and DNA methylation involves the addition of a methyl group which is a carbon with three hydrogen's to the cytosine DNA nucleotides by an enzyme appropriately called methyl transferase and this typically occurs in cytosine rich sequences called CPG Islands don't forget that cytosine pairs with G guanine so that's why there are cg islands that you'll find DNA methylation stabili alters the expression of genes and so it occurs as cells divide and differentiate from embryonic stem cells into specific tissues and so this is essential for normal development and is associated with other processes such as genomic imprinting and X chromosome inactivation topics for another discussion and abnormal DNA methylation has been implicated in carcinogenesis or the development of cancer so you can see how the normal functioning of DNA methylation is a critical regulatory mechanism for our cells now DNA methylation may affect the transcription of genes in two ways first the methylation of DNA itself may physically impede the binding of transcriptional proteins to the gene and second and likely more important methylated DNA may be bound by proteins known as methyl cpg binding domain proteins or MB DS for short now MBD proteins can then recruit additional proteins to the locus or a particular location in a chromosome certain genes such as histone deacetylases and other chromatin remodeling proteins and this modifies the histones forming condensed inactive heterochromatin that is basically transcriptionally silent
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