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14

From a brief survey of the literature, it seems Kawasaki and Taira have been largely vindicated by the community before and since their paper. The retraction was by Taira alone, Kawasaki refused to co-sign because he maintained the data were valid. From the retraction it seems the reason for the retraction was a lost lab book. Prior to the Kawasaki and ...


12

Sort of like having one of these: instead of this: Surely you could simply wrap DNA up in a coil, but to do it in a neat fashion that allows you to package and repackage sections as needed, it's a lot better to have some dedicated machinery. It is also difficult to organize DNA without a supporting structure because the negative charge of the DNA polymer ...


8

As already mentioned by Stefan, the "histone" code is not really a universal code; it is restricted to eukaryotic systems and even then, not unambiguous. It is, at present related to two kinds of histone modifications and their correlation with the transcriptional activity at that locus: Methylation Acetylation Other modifications such as phosphorylation ...


7

The core histones are H2A, H2B, H3, and H4, and the linker histones are H1 and H5. The structure of the nucleosome is well explained in wikipedia: Two of each of the core histones assemble to form one octameric nucleosome core particle, and 147 base pairs of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn. The linker ...


6

According to literature, histone marks seem to be affecting splicing both directly and indirectly.  The indirect regulation appears to be due to biophysical hindrance, where a certain chromatin structure would cause Pol-II slowdown, allowing the splicing machinery to do its job.  The direct regulation seems to be essentially dependent on H3K36me3 and ...


5

See here. Histones are basic proteins (cationic, high pI) because they are required to interact with polyanionic DNA at physiological pH. Heparin and dextran are polyanions which form insoluble salts with the cationic histones.(Dextran is a polymer of glucose. In dextran sulphate it is derivatised with sulphonate groups creating a polyanionic material.) ...


5

Jon Wilkins has a nice introduction to imprinting. He does a nice job of introducing the idea methylation and how these patterns are maintained during development and cell division. Further, he links to some interesting papers on the subject.


4

"Are these modifications the primary regulation mechanism for chromatin structure?" It depends on how you define primary, we might currently think of histone modifications as primary because other regulatory mechanisms have not yet been well studied. Something else you can think of are the various regulatory proteins that interact with histone marks to ...


4

The histone code isn't a sequence of letters like you see in DNA and RNA but rather refers to the pattern of post-translational modification of histones. This is then, by definition, an epigenetic control of gene expression. Histones are basic DNA binding proteins around which DNA is wound to form chromatin. For transcription to occur, transcription factors ...


4

B-form DNA is wrapped around histones in a left-handed manner resulting in a left-handed solenoidal superhelix (see that, that and this). The reason for this wrapping is that it reduces the helical tension. This post has more information about DNA helical tension. Also note that exceptions exist (i.e. right-ended direction) especially for histone at the ...


4

Why DNA needs histones to be packaged and ordered? Histones counteract retroelements, and this defense against parasitic (viral) DNA is presently considered to be their original physiological role. see: Madhani, Cell, 2013: "The Frustrated Gene: Origins of Eukaryotic Gene Expression" Why DNA needs histones to be packaged and ordered ? Why DNA cannot do ...


3

Yes, they have to. But that is just half of the story. The (canonical) histones which are used in DNA replication are synthesized at the beginning of the S phase, and subsequently transported into the nucleus. Studies have shown that newly synthesized DNA is immediately packed into nucleosomes. Thus, it is necessary that these structures are available prior ...


3

It is difficult to draw any conclusion without further experimentation. There may be many other factors that prevent the expression of the gene including factors like post-transcriptional regulators. Some histone modifications like the ones you are mentioning are also a bit dicey and there can be bivalent modifications too. However, if there is a strong ...


3

This is the best review I have seen with a comprehensive discussion on gene duplication and amplification mechanisms (and it is also quite recent). It seems like there may be no definitive answers to your question in the literature--perhaps because of a paucity of viable experimental models that would allow one to test various hypotheses. Also @canadianer ...


2

I can get the ball rolling.. Found a nice paper which looks at this phenomenon in yeast. So as a primer, 8 histone proteins come together to make a spool of sorts which DNA wraps around: Histone proteins have many sequence variants, and each one of them can be covalently modified with methyl, acyl, phospho, SUMO, adp and many other sorts of chemical ...


2

In early embryogenesis, cell division called cleavage occurs every 30 min and there is no transcriptional activity. Oocytes have accumulated important gene transcripts and synthesize the proteins at right times. However, histone is one of the most abundant proteins and it would be difficult to supply enough histone proteins during early embryogenesis while ...


2

First off let's define some concepts. DNAse hypersensitive regions are DNA regions which are in an open chromatin conformation (i.e. euchromatin). This means that those regions are more active at the genomic level (i.e. higher gene expression, gene regulation and higher TF binding) and are less prone to form nucleosomes. Histone mark sites are DNA regions ...


2

Cis-regulatory elements are simply DNA regions upstream or downstream of a gene that can affect its expression (basically they have to be in the same chromosome). DNAse-I hypersensitive sites (DHS) are regions of chromatin that get digested during the DNAse treatment because they are exposed i.e. not protected by a protein (complex). The protein complex can ...


2

In Molecular Biology of the Cell (Chapter 4), it is written that The major histones are synthesized primarily during the S phase of the cell cycle and assembled into nucleosomes on the daughter DNA helices just behind the replication fork (see Figure 5–32). In contrast, most histone variants are synthesized throughout interphase. They are often inserted ...


1

The "histone code" is not like the genetic code where one codon in an ORF always is translated to a single amino acid. It's closer to something like GC content or CpG islands: a single instance doesn't tell you anything, but enrichment over some finite window may be biologically significant. You may want to review the basics, starting with the Wikipedia ...


1

For histone methylation , whether the marks are activating or repressive is determined predominately by which histone tail is modified at which position. DNA methylation by itself however is position dependent; in regulatory regions such as enhancers and promoters methylation tends to be repressive (at enhancers this is mostly mediated by being ...


1

The first thing that comes to mind for me is that the transfer seems excessive... isn't histone sub-20 kDa? I have often transferred similar-sized proteins at 4C for 30 min, 30V. In general, presence of SDS will inhibit transfer efficiency, and increasing alcohol in your TG buffer will counteract the effect of SDS present. Perhaps bring down the methanol ...


1

The authors obviously meant to write that the histones associated with the promoter become deacetylated. They cannot mean the promoter itself as that is DNA. What they wrote is not shorthand or acceptable alternative usage, but just a mistake — published papers often contain typos and mistakes of this sort. Probably the authors meant to write the ...


1

We have a more recent study, Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin and they seem to suggest that in accordance with your '05 paper, H3K36me3 in part contributes to the formation of tightly packed, inaccessible chromatin. You'll see there's a lot of crosstalk, but you would also think that ...


1

ChIP-seq isn't perfect. Even between technical replicates, you get a fair amount of variation, especially for broad marks like those you're using. It's rather uncommon to see people use H3K79me2 and H3K36me3 to determine if a gene's expressed or not. Using H3K4me3 and H3K27ac or H3ac is a more common method of marking promoters of transcribed genes. 40 ...


1

Keep in mind that it is not individual histones that are binding, there are 8 histone proteins forming a compact nucleoside particle, and the particle has 146 bp of DNA tightly wrapped around it. Since the interaction between the histones and the DNA are not sequence-specific, it is unlikely that a single nucleotide polymorphism would have a measurable ...


1

Histone methylation is regulated by a variety of of events, including transcriptional activation and repression, relative location of the histone in the chromatin (pericentric or not, hetero- vs. euchromatin, etc.), X-inactivation, the cell's point in the cell cycle, and others. A variety of signaling pathways can lead to the (in)activation of HMTs. I found ...


1

First we must remember what a nucleosome is: a segment of DNA packed with proteins called histones. This is the initial step to turn the DNA a more compact structure. Citing the advantages of an extremely compact but flexible structure like chromosomes would make this answer a little longer (if you want, I can add them later), and to answer your question ...


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