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12

Here I will assume we are talking about eukaryotic sequence specific transcription factors (ssTFs) and try to answer your first and part of the second question. There is in any case not definitive answer yet. An estimate of ssTFs genes in humans is given in the 2009 Nature Reviews Genetics paper by Vaquerizas, JM et al, A census of human transcription ...


12

The NF-κB family of transcription factors is very modular, with different combinations having different effects. The active (nuclear, DNA-bound) TF is a dimer, composed variously of RelA/p65, RelB, c-rel, NFKB1/p50, and/or NFKB2/p52 subunits. For example, the "canonical" p65/p50 dimer is activated in response to stimulants like TNF-α (tumor necrosis factor ...


10

You can validate the interactions by knockding down (KD) or overexpressing (OE) a gene and checking the change in expression levels of the downstream nodes. You can do this in a high throughput fashion using microarray or RNAseq. For protein you can do an LC-MS. However this method cannot help you in: Differentiating direct vs indirect interactions Finding ...


9

For a free resource, try GenMAPP. Commercial products like Ingenuity Pathway Analysis do the same thing with prettier graphics and a curated approach to network-building, but access can be expensive if you're not affiliated with an institution that will foot the bill.


9

Okay, I'll take this out of the comments and put in an answer for all of us to work on. To directly answer your question: "Is there an estimate for the percentage of these genes whose primary function is related to regulation of gene expression?" It depends on how you define "gene expression." And what cellular processes you want to include in ...


9

Yes, these sequences exist and they are called "silencers" (surprising, right?). There are different mechanisms by which this silencing of genes can happen. In the "classical" way the silencer is bound by a transcription factor which either passively suppress the gene by hindering the binding of specific transcription factors or by actively preventing the ...


7

Yes, look at FANTOM and their work. There are about 2000 transcription factors and co-factors in the human genome. These are proteins, of course. If you add a couple (or few?) thousand microRNAs and a few dozen anti-sense transcripts, although small in size, you inch that percentage upwards. With some 70% of the human genome transcribed, by some estimates, ...


7

Housekeeping genes aren't clustered on a single chromosome. It is perhaps not that 'housekeeping' genes - broadly expressed genes - are 'above the laws of regulation'; rather that their regulation is merely more straight-forward than that of specialised genes. I can think of 2 factors that could be relevant: Abundance of methylation sites (CpG sites) ...


6

If you can't afford ingenuity, KEGG has branched out into regulatory networks as well. Here's the link to their version of the pathway. http://www.genome.jp/kegg/pathway/hsa/hsa04115.html Its free to use as a reference and for academic research.


6

The problem with housekeeping genes is that they are often not stable and their expression depends on the cell types as well as the conditions. They can be stable under one condition, but are not under another. So this needs to be tested every time you have to choose a housekeeping gene - always use GAPDH or beta-Actin simply doesn't work or skews the ...


6

Yes, nucleosomes are completely unwound. Histone chaperones such as FACT (for H2A/H2B) and ASF1, CAF-1, HIRA, Nucleophosmin etc (for H3/H4), associate with RNA Pol II and handle the displaced nucleosomes. As you surmised, the histone octamer complex is disassembled, into the H3/H4 tetramer and two H2A/H2B dimers. Right behind the elongating Pol II, the ...


5

Here are some examples: electric oscillators: neural activity cardiac automatism (0.8 ... 1 Hz) mechanical oscillators (as a result of neural activity): heart beats breathing (0.2 ... 0.3 Hz) intestinal peristaltic waves vocal chords activity (up to a few kHz) muscular spasm (pathological) chemical oscillators: insulin variation in concordance with ...


4

As you no doubt know, the term operator was coined by Jacob and Monod as part of the formalism they developed to explain the properties of certain mutants in the lac operon in E. coli. In physical terms it is indeed the site of binding of a transcription factor, the lac repressor. My understanding is that technically it is best to restrict the use of this ...


4

There was a paper published in Cell last year that has shown that the binding motif of a Hox transcription factor will change depending on whether there's a co-factor bound to the Hox. Slattery et al. (2011) Cofactor Binding Evokes Latent Differences in DNA Binding Specificity between Hox Proteins. Cell, 147(6) 1270-1282. doi: 10.1016/j.cell.2011.10.053 ...


4

Here are 3: 1) gene knockout. Just delete the gene from the genome. The function is gone - useful for demonstrating a direct involvement of the gene in the phenotype. As a phenotype, the microarray will register all sorts of reactions to the loss of the gene in addition to the RNA in question being gone. 2) use selection to find mutants for the gene. ...


3

Positive co-operativity without feedback from the downstream genes: I guess Polycomb/Trithorax complexes will fit this criterion nicely. Polycomb group (PcG) represses Hox and other differentiation related genes (such as neurogenin) while Trithorax (TrxG) group promotes their expression. They are not like usual transcription factors that bind to promoters ...


3

There's no rule that says a transcription factor must be either a repressor or an activator. The lambda repressor (CI) is in fact a repressor and activator of transcription, depending on where it is bound and to what promoter you are referring to. I know your question isn't directly about lambda phage, but I think this mechanism may be best explained in the ...


3

I'm tempted to say, "It's complicated." CI does indeed act as both a repressor and activator. Transcription regulation in the lambda bacteriophage is quite complex for such a small system, so some confusion is understandable. Lewis et al. gives a rough description in a relatively recent paper (1): The CI protein autoregulates its synthesis. At low ...


3

So what you need is basically your data expressed as counts instead of proportions. Even if you do not have the matrix of counts as raw data, these proportions only needs to be multiplied by the total number of binding sites used in the study (e.g. the number of sequences that have been analysed) to get the counts (since proportion = count/total number of ...


3

This probably isn't the complete answer as I don't know so much about eukaryotic transcription, but maybe I can start the answer. First of all DNA bending can be sequence dependent - the double helix is not intrinsically straight. DNA is also pretty easy to bend - it spends most of its time coiled pretty easily around histones, and eukaryotes, supercoiled ...


3

Inferring transcriptional / regulatory networks from empirical data is an active area of research, and to my knowledge there aren't many mature tools for this type of analysis. I see mostly mathematicians, statisticians, and engineers working on this problem, probably because of the intense quantitative theory involved. Even if mature tools do exist, I doubt ...


3

If you have control expression values $c$ and e.g. disease expression values $d$, you take the ratio: $\frac{d}{c}$. If this is greater than one, it's up-regulated. Usually, the log-ratio is computed: $log\frac{d}{c}$. Now, if this is positive, the gene is up-regulated. Gene expression values are usually measured genome-wide and then normalized before ...


2

Is there any relationship between DNA methylation as a level of stability to epigenetic states and genome size? I would say yes, because methylation is used to disable genes in differentiated cells. Disabled genes in differentiated cells generally need to stay disabled to maintain normal behavior for the cell type. Larger genomes usually encode more ...


2

Removal of 5' cap is essential for degradation by 5'→3' exonucleases such as Xrn1/2. Xrn1/2 is constitutive and degradation of uncapped RNAs would be quite fast (don't have a reference for the exact lifetime). Deadenylation generally precedes 3'→5' degradation by exosome but I am not sure if that is a prerequisite. However tailless mRNAs can be stabilized by ...


2

I can answer this question only based on guesses because I am not really sure about your claim that activators are higher in number than repressors. So consider this as an extended comment. While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit ...


2

Heterochromatin profile is of course different in different cells but I am not sure if absolute heterochromatin content will vary greatly. This DNAse hypersensitivity region data is for human cells but same principles apply to all organisms. If I have to take a guess then I would say that quiescent cells are likely to have more heterochromatin. ...


2

Your logic looks correct to me. Essentially, what you are doing is uniformly distributing the regulator among the available mRNA. Note that even when using Hill functions to model transcription, the ratio of transcription factor (TF) concentration to the number of TF binding sites must be large - otherwise, you would have to consider binding ratios even at ...


2

Since @biogirl has given an answer, I'll add my opinion: β-galactosidase would be expressed but the permease and transacetylase would not. The operator lies adjacent to/slightly overlaps the promoter, upstream of the lacZ gene. Binding of the repressor to the operator blocks the promoter, and induction of theoperon involves the repressor leaving the ...


2

Interesting question. I think I have two examples for you which might be interesting. The first is the co-regulation of the microphthalmia-associated transcription factor (MITF) in pigmentation by SOX10 and PGC1a/b. See this paper: PGC-1 coactivators regulate MITF and the tanning response. The second is about the regulation of brown fat tissue by PGC1a ...


2

Enhancer is a just a term for a regulatory region distant from a gene that contains specific sites where transcription factors bind. As it happens, a single enhancer can contain DNA binding sites for multiple transcription factors. For example, an enhancer called TESCO, which regulates a gene called SOX9 (involved in sex determination) has binding sites ...



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