21

The paper by Lobo and Levin is an attempt to learn a model that represents the inner workings of a biological system by fitting parameters to data. This is a common topic in "systems biology", a model-based approach to studying biology that is popular in some fields. Even for small systems, this is a phenomenally hard problem. Unlike most machine learning ...


20

The fruit, sadly, does not hang so low. Short version Lobo et al (the work you refer to) is a nice and not especially novel application of basic Systems Biology modeling approaches to the wound healing system in flat worms. The main barrier to the wider application of such work is the lack of the necessary experimental data. Lobo et al themselves don't ...


13

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 ...


11

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 ...


10

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 ...


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

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

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

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 ...


6

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 ...


5

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 ...


5

People often imprecisely say that type of regulation takes place on the order of many minutes to hours, and that may be as precise as you can get given the variable kinetics of any given pathway. Also, all genes in eukaryotes require general transcription factors, but basically all of them also require activators to act first to recruit the GTFs and ...


5

There is no fundamental difference between viral RNA and and native cellular RNA other than the sequence of RNA bases in them. The sequence differences are not biochemically apparent in the RNA, only in the protein products produced from the RNAs. Regulation of native RNA is done in a huge variety of ways (nothing in the cell is designed; everything is ad ...


4

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 ...


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

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

I highly recommend you to visit Pathguide to get a sense of how vast is the catalog of Pathway Databases. Looking into the category Pathway Diagrams or in Transcription Factors / Gene Regulatory Networks should help in your task. I would start by looking at these DataBases: GeneMania BioCarta WikiPathways Reactome If you are working with a species other ...


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

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

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 ...


3

Christian, great idea to ask this question here before taking important decisions. Are those media articles a hype? Yes. Over the last 10 years I constantly see those hype stories in media about "revolutionary" large-scale-study/big data projects with mind-blowing numbers (gigabases, teraflops, terabytes, thousands of papers and hundreds of genes). ...


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

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 and ...


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 co-...


2

You nailed down what enhancers are (canadianer give a good explanation too, while not answering the question in my opinion). For understanding the authors statement you first need to know that: Lineage-specific and signal-dependent transcription factors are specific classes of transcription factors. Those are TFs that require external signals for ...


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 ...


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

Just to add very recent new information to the first answer: the initial steps of RNA Pol II transcription through a nucleosome have now been revealed at the structural level by cryoEM. See these two articles: https://doi.org/10.1126/science.aau9904 https://doi.org/10.1101/437574


2

Chromatin immunoprecipitation (ChIP) or ChIP-Seq are the first methods that pop into my mind. Essentially, DNA is cross-linked to bound proteins (transcription factors, histones, etc.) by various methods, then broken into pieces by either sonication or digestion with micrococcal nuclease. An immunoprecipitation is then performed by adding antibodies ...


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