Posts Tagged ‘chromatin’
epigenetics at the very beginning of life – my explorations
So let me see if I can understand epigenetics through other sources, and through what I’ve read so far. First, it’s essential for the very first cell divisions in human – or shall we say mammalian – life, at least for placental mammals. Their lives begin with a fertilised egg, a sperm cell and an egg cell (both known as gametes), each with its complement of DNA (but the egg cell contains much more, and there’s a difference between an ovum and an oocyte, which I won’t go into, as if I could). This cell, also known as a zygote, is the ultimate totipotent stem cell, potentially able to form every type of somatic (diploid) cell. So what causes this cell to divide and multiply, and become, in a few days, a blastocyst?
A blastocyst is already quite a complex collection of cells, with an outer layer, the trophectoderm, an inner cell mass, and a blastocoel, which is a fluid-filled cavity. So, already quite a jump from a zygote, so I need to know how that happens. But even before that, I need to know how a zygote comes into being. Wikipedia puts it this way:
The formation of a totipotent zygote with the potential to produce a whole organism depends on epigenetic reprogramming. DNA demethylation of the paternal genome in the zygote appears to be an important part of epigenetic reprogramming.
That doesn’t help too much, but I’m guessing that this ‘epigenetic reprogramming’ thing is what creates cell diversity – but this description tells us that the formation of the zygote is itself an epigenetic product. Here’s another description of the first steps:
The four stages of embryonic development include fertilization (zygote formation), cleavage (rapid cell division), blastocyst formation, and finally, implantation into the uterine lining.
Cleavage? The website I filched this from (ferty9.com, listed below) fails to elaborate, and looking up the word an sich just takes me to female breasts, which is pleasant but distracting. AI (never lies) gives more detail, claiming four cleavage stages, 1. the zygote stage, 2. the 2 to 8 cell stage, 3. the morula stage, and 4. blastocyst formation. And presumably epigenetics plays a role in the move from one stage to the next?
So, I’ve tracked down a most sciencey article, from ScienceDirect, entitled ‘Epigenetic regulation of early human embryo development’, which I hope to make sense of. Its opening paragraph is a bit daunting though:
Epigenomes undergo profound change during the first few days of embryonic development. The resetting and establishment of epigenomes are coordinated within and contribute to the wider processes of embryogenesis. As a consequence, faithful epigenetic regulation is required to safeguard development and to establish long-lived epigenetic states that have effects on genome function throughout the life course.
So now we have epigenomes, and here’s a definition:
Epigenome: The epigenome consists of all the chemical modifications of DNA and histones of a cell/organism that contribute to regulate gene expression independently of DNA sequence.
Histone modification involves the post-translational modification of specific amino acids that influence the overall structure of histone proteins. Changes in histone structure may then influence their function, resulting in incomplete DNA unwinding that may also effect transcription activity. Major histone modifications include acetylation, methylation, phosphorylation, ubiquitylation, and, less frequently, ribosylation, sumoylation, and citrullination
References
https://pmc.ncbi.nlm.nih.gov/articles/PMC4783933/
https://www.sciencedirect.com/science/article/pii/S153458072101042
https://embryology.med.unsw.edu.au/embryology/index.php/Blastocyst_Development#Introduction
https://www.sciencedirect.com/science/article/pii/S1934590923003314
Epigenetics 8: some terms
The gene is not more ‘basic’ than the organism, or closer to ‘the essence of life’, whatever that means. Organisms have DNA codes, and they maintain external forms and behaviours. Both are equal and fundamental components of being. DNA does not even build an organism directly, but must work through complex internal environments of embryological development, and external environments of surrounding conditions. We will not know the core and essence of humanity when we complete the human genome project.
Stephen Jay Gould, ‘Magnolias from Moscow’, in Dinosaur in a Haystack, 1996
I remember ages ago promising that I’d start every blog piece with a quote, then I more or less immediately forgot about it. Anyway the above quote kind of refers to epigenetics, and anticipates, in a way, the disappointment that many have felt about the human genome project and its not-quite-revelatory nature. As we learn more about the complexities of epigenetics, more about the relationships between genotype and phenotype will be revealed, but the process will surely be very gradual, though relentless. But I can’t talk, knowing so little. In this post, I’ll look at a very few key terms to help orient myself in this vast field. Not all will be specifically related to epigenetics, but to the whole field of DNA and genetics.
nucleosome: described as ‘the basic structural form of DNA packaging in eukaryotes’, it’s a segment of DNA wound round a histone ‘octamer’, a set of eight histones in a cubical structure. All of this is for fitting DNA into nuclei. Nucleosomes are believed to carry epigenetic info which modifies their core histones, and their positions in the genome are not random. Each nucleosome core particle consists of approximately 146 base pairs.
chromatin: a complex of DNA and protein, which packages DNA protectively, condensing the whole into a tight structure. Histones are essential components of chromatin. Chromatin structure is affected by methylation and acetylation of particular proteins, which in turn affects gene expression.
nucleotides: the basic building blocks of DNA and RNA, they consist of a nucleoside and a phosphate group. A nucleoside itself is a nitrogenous base (also known as a nucleobase) and a five-carbon sugar ribose (a ribose – these explanations always need more explaining – is a simple sugar, the natural form of which is D-ribose, and which comes in various structural forms). DNA and RNA are nucleic acid polymers made up of nucleotide monomers.
nucleobase: a nitrogenous base (e.g. adenine, cytosine, thymine, guanine, and uracil which replaces thymine in RNA), the fundamental units of our genetic code. Also simply known as a base.
base pairs: a base pair, in DNA, is one of the pairings adenine-thymine (A-T) or cytosine-guanine (C-G). They are pyrimidine-purine pairings. Adenine and guanine are purines, the other two pyrimidines. Due to their structure pyrimidines always pair with purines.
CpG islands: regions of DNA with a high frequency of CpG (C-G) sites, i.e. sites where a cytosine nucleotide is followed by a guanine nucleotide in linear sequence in a particular direction.
histones: highly alkaline proteins, the chief proteins of chromatin, and the means of ordering DNA into nucleosomes. There are four core histones, H2A, H2B, H3 and H4. These form an octamer structure, around which approximately 146 base pairs are wound.
Obviously, I’m very much a beginner at comprehending all this stuff, but I note that the number of videos on epigenetics seems to increase almost daily, which is raising my skepticism more than anything. I try to be selective in checking out these videos and other info on the topic, as there’s always this human tendency to claim super-solutions to our problems, as in super-foods and super-fitness regimes and the like. I’m more interested in the how of things, which is always a more complicated matter. Other information sources tend to assume knowledge or to skate over obvious complexities in a facile manner, and then of course there’s the ‘problem’ of being a dilettante, who wants to learn more about areas of scientific and historical knowledge often far removed from each other, and time’s running out, and we keep forgetting…
So anyway, I’ll keep plodding along, because it’s all quite interesting.