What controls the mechanism to turn genes on or off? Well there are numerous levels of control as I have said all along. First a transcription factor has to be turned on in some circumstances (other genes transcription factors are always on)sometimes they turn on or off in response to an external signal. This transcription factor has an amino acid sequence that will bind to a specific DNA sequence in the ‘promoter’ region of the gene. Once bound to the promoter of the gene the transcription factor will recruit RNA polymerase. RNA polymerase is the STAR of this Thread! Unfortunately he got billed under TRANSLATION when he does TRANSCRIPTION. RNA polymerase has phosphorylation sites that control which transcription factors it might interact with preferentially and THIS is a COOL discovery! (but it isn’t a new code and it isn’t translation). RNA polymerase makes an mRNA transcript of the gene that then gets spliced into a message and taken to where it needs to get TRANSLATED by use of the 5’ leading edge of the mRNA. The mRNA gets translated into a protein at the ribosome, it has a sequence that initiates this ribosomal binding and some are stronger than others. Once the protein gets made sometimes it binds to the transcription factor that turned the gene on and then turns it off by inactivating its own transcription factor (negative regulation). Sometimes a protein is made and held inactive by another protein and it doesn’t actually do its job until something signals its parter to let go and then it becomes active. Sometimes the body makes a protein and then immediately destroys it because it isn’t needed (but when it is needed, it is too late to signal the DNA to make RNA to make protein, you need the protein NOW!). Those are all levels of control that someone could claim was a ‘code within a code’ or a ‘code upon a code’ but really there is just one code and many many multiple levels of control.
So what was your thesis on?
==Those are all levels of control that someone could claim was a ‘code within a code’ or a ‘code upon a code’ but really there is just one code and many many multiple levels of control.
It would appear that you are at odds with the entire field of epigenetics. There are indeed codes upon codes—GGG
“Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response”
http://www.genesdev.org/cgi/content/full/20/11/1405
These dynamic, “histone code”-driven interactions can represent the sequential order of step-to-step transitions during transcriptional initiation.
http://www.genesdev.org/cgi/content/full/20/11/1405
“From recent work, it is becoming increasingly clear that these modifications form a histone code that regulates chromatin function through their ability to recruit specific interacting proteins that recognize a single or combinatorial set of modifications(Strahl and Allis 2000; Turner 2000; Jenuwein and Allis 2001).”
http://www.genesdev.org/cgi/reprint/17/5/654.pdf
Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly.
[My paper] J Nakayama , J C Rice , B D Strahl , C D Allis , S I Grewal
“The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys9) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys9 methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys9 methylation. Moreover, an H3-specific deacetylase Clr3 and a beta-propeller domain protein Rik1 are required for H3 Lys9 methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a “histone code” essential for the epigenetic inheritance of heterochromatin assembly.”
http://lib.bioinfo.pl/pmid:11283354
“We interpret these modifications in light of previously published data and propose a new and testable model for how cells implement the histone code by modulating nucleosome dynamics.”
http://www.ncbi.nlm.nih.gov/pubmed/15523479
“These findings assign a biological function to this amino acid and highlight a gene type–specific requirement for a residue within the CTD heptapeptide, supporting the existence of a CTD code.”
http://www.cipsm.de/en/publications/researchAreaD/index.html?style=0
OLD DOGS, NEW TRICKS
“S. Grewal (Cold Spring Harbor, NY) presented an elegant combination of genetics and biochemistry that focused on how modifications of the histone tails regulate one another in the establishment of heterochromatin in fission yeast. Grewal showed that deacetylation of lysine 14 (K14) on histone H3 is required for the subsequent methylation of K9, which in turn recruits Swi6, the Schizosaccharomyces pombe equivalent of HP1. The elucidation of this epigenetic pathway not only defines the sequence of events that establish heterochromatin, but also establishes a revolutionary ‘histone code’ (Nakayama et al., 2001), in which modifications of the histone tails carry information for the regulation of gene expression.”
http://www.nature.com/embor/journal/v3/n3/full/embor204.html
Translating the histone code.
Jenuwein T, Allis CD.
Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter, Dr. Bohrgasse 7, A-1030 Vienna, Austria. jenuwein@nt.imp.univie.ac.at
“Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a “histone code” that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.”
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11498575
“Gene transcription occurs on a nucleosomal template known as chromatin. The recruitment of the transcriptional regulators and the transcription machinery to promoter chromatin is coordinated by a genetic code on the DNA and an epigenetic code on the histone proteins.”