Biology Epigenetics Watch

Rockgo288
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So, I’ve learnt that oestrogen can switch on gene by binding to receptor site on transcriptional factor and so this cause the DNA binding site on the factor to change shape and bind to DNA causing the gene to be transcripted and expressed.
And now I’ve also learnt that there are tags on DNA and histones called epigenome. The epigenome determine the shape of the DNA-histone complex and so switch genes on or off. The epigenome is also affected by environmental changes.
My question is:
So, there are two factors that affect our genes expression? One is caused by the hormone oestrogen and the other is environmental factor? That means the two factor both affect gene expression at the same time?
OR
The epigenome cause DNA-histone complex to unwrap/wrap up so transcriptional factor activated by oestrogen can bind/can’t bind to DNA and cause transcription so gene is expressed/not expressed? This means even if oestrogen activate a transcriptional
factor, if the DNA-histone complex is wrapped up by the epigenome, the gene still can’t be switched on? In other words, the epigenome alone determines whether gene is switched on or not?
I know this is too long XD but someone pls help me!!!! Thanks!!!!
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Jpw1097
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That is a very good question. As you've said, oestrogen binds to the oestrogen receptor (ER), which is a nuclear receptor as oestrogen is a steroid, and therefore is lipid-soluble/lipophilic such that it can diffuse directly into the cell. The ER then dimerises with another ER, and this dimer then binds to the oestrogen response element in the promoter region of the target genes, this causes transcription factors to bind and target genes are transcribed. But as you've said, gene expression is also regulated by epigenetic changes such as histone modification (methylation, acetylation, phosphorylation, etc.) and DNA methylation, which can be influenced by the environment. Epigenetic changes ultimately determine whether a gene can be transcribed or not because it alters how tightly packed the DNA is which affects binding of the transcriptional machinery, however, just because it can be transcribed does not mean that it will, this depends on whether the appropriate transcription factors are activated. So in this oestrogen example, the transcription of oestrogen-responsive genes depends on whether the epigenetic changes allows for transcription to take place and, if they can, it also depends on oestrogen binding to the ER. However, binding of oestrogen to the ER can induce epigenetic changes which can permit gene activation. Therefore you need both, an epigenome that permits activation of the genes and the ligand-dependent (oestrogen) activation of the genes. The activation of oestrogen-responsive genes is important is oestrogen-driven cancers, breast, ovarian and endometrial cancers, however, most work has been focused on the oestrogen receptor and Tamoxifen is used in the treatment of ER+ breast cancer as it binds to and blocks the ER on cancer cells. However, it may also be possible to alter the epigenetic changes by modifying enzymes such as methyltransferases, demethylases, acetyltransferases, deacetylases, etc. to reduces transcription of oestrogen-responsive genes. I have included links to a couple papers below if you're interested.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901989/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147309/
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Rockgo288
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(Original post by Jpw1097)
That is a very good question. As you've said, oestrogen binds to the oestrogen receptor (ER), which is a nuclear receptor as oestrogen is a steroid, and therefore is lipid-soluble/lipophilic such that it can diffuse directly into the cell. The ER then dimerises with another ER, and this dimer then binds to the oestrogen response element in the promoter region of the target genes, this causes transcription factors to bind and target genes are transcribed. But as you've said, gene expression is also regulated by epigenetic changes such as histone modification (methylation, acetylation, phosphorylation, etc.) and DNA methylation, which can be influenced by the environment. Epigenetic changes ultimately determine whether a gene can be transcribed or not because it alters how tightly packed the DNA is which affects binding of the transcriptional machinery, however, just because it can be transcribed does not mean that it will, this depends on whether the appropriate transcription factors are activated. So in this oestrogen example, the transcription of oestrogen-responsive genes depends on whether the epigenetic changes allows for transcription to take place and, if they can, it also depends on oestrogen binding to the ER. However, binding of oestrogen to the ER can induce epigenetic changes which can permit gene activation. Therefore you need both, an epigenome that permits activation of the genes and the ligand-dependent (oestrogen) activation of the genes. The activation of oestrogen-responsive genes is important is oestrogen-driven cancers, breast, ovarian and endometrial cancers, however, most work has been focused on the oestrogen receptor and Tamoxifen is used in the treatment of ER+ breast cancer as it binds to and blocks the ER on cancer cells. However, it may also be possible to alter the epigenetic changes by modifying enzymes such as methyltransferases, demethylases, acetyltransferases, deacetylases, etc. to reduces transcription of oestrogen-responsive genes. I have included links to a couple papers below if you're interested.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901989/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147309/
So, in other words, hormones and epigenome both affect gene expression but in my example of oestrogen, if oestrogen activated transcriptional factor but epigenome doesn’t allow transcription to take place, then gene is not expressed. So, in this example, the epigenome is the ultimate factor that determine whether gene is expressed or not.
But, looking from another side, even if epigenome allow transcription to take place, it depends if the specific transcriptional factor is activated by oestrogen so it can cause gene expression. So, in this case, hormone is the ultimate factor that determine gene expression.
Am i right? Thanks for your explanation! it is really helpful!!!
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Jpw1097
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(Original post by Rockgo288)
So, in other words, hormones and epigenome both affect gene expression but in my example of oestrogen, if oestrogen activated transcriptional factor but epigenome doesn’t allow transcription to take place, then gene is not expressed. So, in this example, the epigenome is the ultimate factor that determine whether gene is expressed or not.
But, looking from another side, even if epigenome allow transcription to take place, it depends if the specific transcriptional factor is activated by oestrogen so it can cause gene expression. So, in this case, hormone is the ultimate factor that determine gene expression.
Am i right? Thanks for your explanation! it is really helpful!!!
Yes, at least that's my understanding. But also be aware that oestrogen binding to the ER can also cause epigenetic changes which facilitate binding of the transcriptional machinery to the gene, by altering the activity of various enzymes - so it gets a bit complex.
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Rockgo288
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(Original post by Jpw1097)
Yes, at least that's my understanding. But also be aware that oestrogen binding to the ER can also cause epigenetic changes which facilitate binding of the transcriptional machinery to the gene, by altering the activity of various enzymes - so it gets a bit complex.
Ok, so all in all, all kinds of factors affect gene expression XD Thanks!!
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