Talk:5-Hydroxymethylcytosine

First revisions

I should disclose that I am a member of the Rao lab (and a middle author on one of the cited papers), and thus had a personal interest in adding our research to the page. That said, we did publish side by side with Heintz in Science and I think our work with the nucleotide warrants inclusion. Certainly the enzyme that generates hmC and it's existence outside of brain cells is of real importance.

I'm thinking of making two more edits, but wanted to see if there are any objections. First, I'd like to remove the part of hmC having a role in brain function. We showed that hmC is present in murine ES cells, and Heintz's paper seems to show hmC in other tissues, around the limit of detectability. Unfortunately TLC just isn't good enough for quantifying hmC levels in most bulk tissues, but it is probably found in many cell types. Yes, it has a role in the brain, but you wouldn't write "glucose probably has a role in the brain function because it is found in the brain." We shouldn't be singling out organs here. I wouldn't object though if someone wanted to write that it likely has a big role in Purkinje neurons, because it is found in truly gigantic quantities there.

Second, I have no problem acknowledging previous work, but I'm thinking of casting some doubt on the Yura (1972) paper or else deleting that paragraph altogether. They claimed that hmC made up as much as 15% of all cytosine in brain and liver, and that 5-mC was barely present in these organs! Mind you, only about 8% of cytosines are followed by guanine. Yura's lab only saw hmC when they extracted DNA via a very unusual technique, and claimed that the reason no one else sees it is because it is degraded during conventional DNA extraction. In fact, hmC is chemically perfectly stable. People have been working with hmC in the context of phage for a long time, and can handle and extract the base without it all magically going poof. And the fact that neither we nor anyone else in the last 35 years has seen complete replacement of mC with hmC in brain and liver makes the Yura data very doubtful. I don't know what was happening there, but they weren't detecting endogenous hmC.

Cheers, Anonymous —Preceding unsigned comment added by 71.232.117.70 (talk) 00:36, 31 May 2009 (UTC)

I have no objections to your thoughts. Dogposter (talk) 00:30, 2 June 2009 (UTC)

Molecular structure

I just noticed that the picture we have for 5-hmC is wrong. N1 should be protonated, not N3. And we should probably have the 5-hmC oriented with N1 at the bottom, the same as the pictures of cytosine and 5-methylcytosine in their respective articles. I'll put up a corrected picture this evening.

Anonymous Rao lab member again —Preceding unsigned comment added by 134.174.6.108 (talk) 23:19, 10 July 2009 (UTC)

Okay, so apparently I have to create a wikipedia account and wait some time before adding images. Will do. In the mean time, I am taking down our current 5-hmC picture. Better no diagram than a wrong one.

Anonymous Rao lab member

The image isn't wrong - it's just a different tautomer than the one you suggest. Both will exist in equillibrium with each other. ChemNerd (talk) 13:07, 15 July 2009 (UTC)

In the context of dNTPs or actual physiological DNA the tautomer featured would not exist in significant quantities. The N1 would be bonded to the ribose and therefore be much less prone to double bond formation. Also, Guanine pairs with Cytosine, and the tautomer featured would NOT pair with guanine (instead of a hydrogen bond forming, you would have hydrogens crashing into each other). If nothing else, we should feature the same tautomer we show for cytosine and 5-methylcytosine. The current picture may technically be correct for the base alone, but it is not as relevant and will confuse innocent biologists. You would never have an article on Cytosine that showed the tautomer incapable of Watson-Crick pairing! I'm going to replace this picture as soon as I can. —Preceding unsigned comment added by 71.232.117.70 (talk) 00:12, 19 July 2009 (UTC)

Oh yes, I think this page should be in the "Molecular and Cellular Biology WikiProject", and this molecule is mainly interesting for its existence in DNA. It's me who has been making these anonymous edits by the way, including the last comment. I just hadn't had an account before and I forgot to sign in just now. —Preceding unsigned comment added by Rotsapsky (talk • contribs) 00:21, 19 July 2009 (UTC)

My apologies, that wasn't meant to sound like a demand or challenge. This molecule is very dear to my heart, I can get a little worked up. —Preceding unsigned comment added by Rotsapsky (talk • contribs) 00:45, 19 July 2009 (UTC)

I'm very confused by this sentence: "Embryonic and neuronal stem cells contain significantly less hydroxymethylcytosine than fully differentiated cells.[8][9]". It seems ambiguous and possibly wrong to me as ESCs have very high content of 5hmC. It's also unclear what type differentiated cells it's talking about. --Juliathedog (talk) 14:26, 13 May 2011 (UTC)

@Juliathedog- I am in agreement with you. Also, the references listed do not appear to directly corroborate this statement. Shadlese (talk) 06:23, 27 May 2011 (UTC)

@Shadlese- I'll go ahead delete that sentence. It seems to me the relationship between changes in the amount of 5hmC and differentiation is not well characterized at this point.Juliathedog (talk) 04:25, 30 May 2011 (UTC)

Rating

Should this really be rated low importance? Dogposter 16:56, 12 August 2009 (UTC) Ok, I'll change it to mid importance because nobody has responded. Dogposter 01:31, 9 November 2009 (UTC)

Citation

The following citation was appended to the end of the article, but does not appear to be for the purpose of supporting article content, so I'm moving it here in case anyone finds it helpful for improving the article: Ruzov A, Tsenkina Y, Serio A, Dudnakova T, Fletcher J, Bai Y, Chebotareva T, Pells S, Hannoun Z, Sullivan G, Chandran S, Hay DC, Bradley M, Wilmut I, De Sousa P (2011). Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development. Cell Res. doi:10.1038/cr.2011.113-- Ed (Edgar181) 22:10, 17 July 2011 (UTC)