H Carey Quotes

You know the song, “Obsessed” by Mariah Carey? I think she knew what she was doing when she wrote it,” she says in place of an answer. My brow furrows. “What?” “I’m just saying, obsession comes with some serious side effects. Might want to keep that in check before you turn into a murderous psycho.” I’m silent for a beat before asking, “Who says I’m not already?” “You could be. Are you here to murder me, Enzo? Is it because I don’t return your affections?” “Baby, if anyone were to become obsessed with you, it would only be for what’s between your thighs, not because you have anything else to offer.” She doesn’t respond.

It has always been in places of barrenness and isolation, where the heart of man begins to perceive that which, in the midst of his fast-paced life, he never could. Removed from the subtle pleasantries and distractions of his work-a-day world, his needs become simplified and yet more urgent; his ears become more sensitive and able to hear those gentle songs of heaven beginning to resonate in his soul. (pg. 59-60)

Some of the normal histones are removed altogether. Histone H2A is replaced by a related but subtly different molecule called macroH2A, strongly associated with gene repression.

The Air ncRNA gave scientists important insights into how these long ncRNAs repress gene expression. The ncRNA remained localised to a specific region in the cluster of imprinted genes, and acted as a magnet for an epigenetic enzyme called G9a. G9a puts a repressive mark on the histone H3 proteins in the nucleosomes deposited on this region of DNA. This histone modification creates a repressive chromatin environment, which switches off the genes.

In this model, there is a vicious cycle of events that results in the generation of a more and more repressed state. One of the predictions from this model is that repressive histone modifications attract DNA methyltransferases, which deposit DNA methylation near those histones. This methylation in turn attracts more repressive histone modifying enzymes, creating a self-perpetuating cycle that leads to an increasingly hostile region for gene expression. Experimental data suggest that in many cases this model seems to be right. Repressive histone modifications can act as the bait to attract DNA methylation to the promoter of a tumour suppressor gene. A key example of this is an epigenetic enzyme we met in the previous chapter, called EZH2. The EZH2 protein adds methyl groups to the lysine amino acid at position 27 on histone H3. This amino acid is known as H3K27. K is the single letter code for lysine (L is the code for a different amino acid called leucine).

What holds cells in this teetering position? In 2006, a group headed by Eric Lander at the Broad Institute in Boston, found at least part of the answer. A key set of genes in ES cells, the pluripotent cells we have come to know so well, were found to have a really strange histone modification pattern. These were genes that were very important for controlling if an ES cell stayed pluripotent, or differentiated. Histone H3K4 was methylated at these genes, which normally is associated with switching on gene expression. H3K27 was also methylated. This is normally associated with switching off gene expression. So, which modification would turn out to be stronger? Would the genes be switched on or off? The answer turned out to be both. Or neither, depending on which way we look at it. These genes were in a state called ‘poised’. Given the slightest encouragement – a change in culture conditions that pushed cells towards differentiation for example – one or other of these methylations was lost. The gene was fully switched on, or strongly repressed, depending on the epigenetic modification

You know the song “Obsessed” by Mariah Carey? I think she knew what she was doing when she wrote it.

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