#histone

[science-sculpt]

The Nucleosome: DNA's Fancy Packaging and Party Trick!

Imagine cramming two meters of yarn into a pea-sized box. Sounds impossible, right? Well, that's the impressive feat that cells pull off every single day with DNA! They use a clever structure called the nucleosome to pack this massive genetic blueprint into the tiny nucleus.

The journey began in 1974 when Don and Ada Olins, peering through an electron microscope, spotted repeating beads – the first glimpse of nucleosomes. Roger Kornberg, building upon this observation, proposed the now-iconic "subunit theory," envisioning DNA wrapped around histone protein cores. This theory, later solidified by Pierre Oudet's term "nucleosome," laid the groundwork for further exploration. The 1980s witnessed a flurry of activity, with Aaron Klug's group using X-ray crystallography to reveal the left-handed superhelical twist of DNA around the histone octamer. But the true masterpiece arrived in 1997 when the Richmond group, armed with advanced techniques, unveiled the first near-atomic resolution crystal structure of the nucleosome. This intricate map, showcasing the precise interactions between DNA and histones, remains a cornerstone of our understanding.

The Players:

DNA: The star of the show, carrying our genetic code in the form of a double helix.

Histones: Protein spools around which DNA tightly winds. Imagine eight of them forming a core, like a mini-protein drum set.

Linker DNA: Short stretches of DNA connecting the spools, like the spaces between beads on a necklace.

The Steps:

Wrap and Roll: Picture DNA gracefully wrapping around the histone core, like thread around a spool. Each nucleosome holds about 146 base pairs of DNA, making about 1.67 turns.

Connect and Repeat: Linker DNA bridges the gap between nucleosomes, forming a "beads-on-a-string" structure. Think of it as pearls strung between the spools.

Compact and Condense: This repetitive unit folds further, creating intricate 30-nanometer fibers. Imagine these as twisted strands of pearls!

Here's the coolest part: histones aren't static. They can be chemically modified, like adding or removing phosphate groups. These modifications act like tiny flags that tell the cell how tightly to wrap the DNA, essentially throwing a "party" for specific genes by making them more accessible. This fine-tuning allows cells to respond to their environment and express the right genes at the right time. Understanding the nucleosome model is crucial for unraveling the mysteries of gene regulation and diseases like cancer. By studying how modifications affect nucleosome structure and gene access, scientists can develop new therapies to target specific genes and potentially treat diseases at the root cause.

While the nucleosome model is the foundation, the story gets even more intriguing. Different histone types and modifications create variations, influencing chromatin structure and function. Think of it as different music genres influencing the dance moves! Additionally, other proteins interact with the nucleosome, adding another layer of complexity to this fascinating choreography.

The nucleosome model is more than just a neat way to package DNA. It's a testament to the intricate dance between molecules that orchestrates life's processes. By understanding this fundamental structure, we gain deeper insights into cellular function, paving the way for advancements in medicine and beyond.

Remember, this is just the beginning! The world of nucleosomes and chromatin is vast and ever-evolving. So, keep exploring, keep questioning, and keep dancing to the rhythm of DNA!

[whats-in-a-sentence]

The fundamental structural unit of chromatin is the nucleosome, an assembly consisting of a group of certain proteins, called histones (designated H1, H2A, H2B, H3 and H4, see figure 25.13a), wrapped in DNA (figure 25.13b). (...) In a nucleosome, B-DNA is wound around the histone unit by about 1.8 coils (figure 25.13b,c). (...) The nucleosomes are further folded to form a filament, with a diameter of ~30 nm, which has been proposed to have the structure down in figure 25.13d.

"Chemistry" 2e - Blackman, A., Bottle, S., Schmid, S., Mocerino, M., Wille, U.

[hoiist]

when the guy you just met is surprised his bluff worked too

[sproutystudies]

Histone Modifications

Hello, hello! Today's topic is histone modifications. We are continuing on with the epigenetics theme after my previous educational post about DNA methylation. As described in that post, epigenetics is the study of heritable genetic modifications without a change in DNA sequence (Takuno & Gaut, 2012). Similarly to DNA methylation, histone modifications affect gene expression through regulation of accessibility of the DNA for transcription (Bartova et al, 2008). But before we get into these modifications, let's go over a bit of background information!

What is a histone, anyway? A histone is a type of protein involved in DNA compaction and organization. In order to fit a genome's worth of DNA into the nucleus of a cell, that stuff needs to be extremely tightly packed! Histones help with this by forming an octomer called a nucleosome, which the DNA wraps around. These nucleosomes then coil together to form a fiber known as chromatin, which goes on to make up a chromosome. When the chromatin is less tightly packed, it is known as euchromatin and it is available for transcription (Bartova et al, 2008). When it is more tightly packed, it is known as heterchromatin, and polymerase proteins cannot access and transcribe the DNA (Bartova et al, 2008). Histone modifications regulate the transition between heterochromatin and euchromatin (Bartova et al, 2008).

(Above image from humanoriginproject.com)

(Above image from Caputi et al, 2017)

The octomer core of a nucleosome is made up of two copies of each of four types of histones: H2A, H2B, H3, and H4 (Marino-Ramirez et al, 2017). Each of these histones includes an N-terminal tail structure, which is the main site of modification (Marino-Ramirez et al, 2017). The tails are modified through addition and removal of certain functional groups or other small structures. Types of modifications include acetylation by histone acetyltransferases, methylation by histone methyltransferases, phosphorylation by kinases, and ubiquitination (Marino-Ramirez et al, 2017). All of this information is used for naming specific histone modifications: Which histone is modified, which amino acid of the histone tail the modification is on, what type of modification is made, and in what amount. For example, H3K9me2 is the name for di-methylation of the 9th Lysine on an H3 histone's tail.

Some important histone modifications and their effects include:

H3K9me2: transcriptional activation + maintenance of CHG DNA methylation in plants

H3K9me3: transcriptional repression

H3K9ac: transcriptional activation

H3K4me1 & H3K4me3: transcriptional activation

H3K27me3: transcriptional repression

H4K16ac: transcriptional activation

H3S10p: DNA replication-related chromatin condensation

(He & Lehming, 2003)

Important Terms: histone, nucleosome, heterochromatin, euchromatin, transcription, epigenetics

[moogfruits]

Hello everybody I am popping on for my first art post in a blue moon

This one took like, 1 hour 10 minutes or something idk I never really bothered enough to count

[simonh]

Translating the Code: A Tale of Tails by National Library of Medicine Via Flickr: Alternate Title(s): Tale of tails Series Title(s): NIH director's Wednesday afternoon lecture series Contributor(s): Allis, C. David. National Institutes of Health (U.S.). Medical Arts and Photography Branch., National Institute of General Medical Sciences (U.S.) Publication: [Bethesda, Md. : Medical Arts and Photography Branch, National Institutes of Health, 2001] Language(s): English Format: Still image Subject(s): Histones Genre(s): Posters Abstract: Predominantly blue poster with multicolor lettering announcing lecture by C. David Allis, Oct. 2001. Series and sponsor information at top of poster. Visual image may be a representation of histone. Title and speaker information on left side of poster. Lecture date, time, and location near bottom of poster. Extent: 1 photomechanical print (poster) : 82 x 46 cm. Technique: color NLM Unique ID: 101455873 NLM Image ID: C02741 Permanent Link: resource.nlm.nih.gov/101455873

[calacuspr]

Ricky Martin – How to become a Director of Football

Not everyone who plays grassroots football is going to make it as a professional player. Even those who secure Academy contracts or break into the reserves or the first team can find themselves not making it at professional level.

Many of them drift out of the game, but with football becoming increasingly big business, there are plenty of opportunities for individuals to carve out a career in the game off the field.

Ricky Martin is one such example. He was an associate schoolboy for Norwich City and played grassroots football for Histon in the Eastern Counties League before getting his break at a young age at Cambridge United.

He explained: “I was a part-time coach at the club and I was running soccer schools so I was like recruiting players for them. When Paul Ashworth was leaving, they interviewed a couple of candidates but the salary package was so low that they couldn't really attract anyone full-time.

“Paul said to the club that I might not seem ready now, but I’d be really good for them and that I was someone that's going to have a career in the game. So I went and met Tommy Taylor, the manager at the time, and they offered me the job.

“At 20, I just knew that I had to get into the game. It was a very different landscape back then that wouldn't happen now. There’s far more structure to sports recruitment and you require a lot of qualifications, which at the time I didn’t have.

“I understand it but the downside is that sometimes clubs don't sometimes take a chance on someone that is up and coming because they need to tick qualifications boxes. You’d now need a lot more experience to oversee a whole youth programme at the age of 20.

“I was leading the whole Academy programme for kids age nine to 18 and some of the players were only two years younger than me. I had five unbelievable years and I wouldn't be where I am today if it wasn't for that opportunity.”

Martin was identifying young talent across East Anglia and securing players who might have gone to Norwich. The Canaries then came calling, appointing him as Assistant Academy Director and then Academy Manager.

The Canaries are a team renowned for developing young talent and Martin’s impact was integral to that success. He was involved in the development of players such as Jacob Murphy, now an integral part of the first-team at Newcastle United, Ben Godfrey who enjoyed a fine spell at Everton before moving to Atalanta in Serie A, and James Maddison, who was plucked from Coventry City and developed before getting moves to Leicester City and Tottenham Hotspur.

Norwich also won the FA Youth Cup, beating Chelsea in the middle of a dominant spell where the west London side won the trophy seven times in nine years. The Canaries also secured Category One status for their Academy, the highest rating in the English youth system.

But football moves forward and so do careers, with Martin keen to take on more responsibility. He explained: “I needed something different and I felt going into a first-team environment was my next step. I needed a new challenge.”

Martin pitched his vision of becoming a Technical Director to the Norwich board, which he secured just as the club was relegated to the Championship at the end of the 2013-14 season.

“The role of the Technical Director was new and is still evolving today. I was there to oversee all the departments. So medical sports, science, operations, recruitment and first team logistics.

“Alongside the manager and the Chief Executive, we formed a management triangle, working side by side. Some clubs put the technical director above the manager, but we wanted a more collaborative approach.

“I assisted the manager to ensure that everything off the pitch was taken care of.  The heads of departments would all report to me and we ensured that we had the right staff in place developing a philosophy of trying to create a best in class environment.”

With varying needs and timelines, juggling each of the departments required delicate management skills to ensure that everything ran smoothly, Martin saw the Canaries get promoted in the Championship play-off final against Middlesbrough before leaving in 2017.

He became a football consultant, advising clubs around the world on various aspects of football administration and youth development.

Within two years, he was back in the Premier League, having been appointed by West Ham, a club renowned for its youth development, as Academy manager.

“When a club like West Ham come calling and gave me an opportunity to lead up their Academy system, it was very exciting and with their tradition and their heritage, it was a great opportunity.

“We managed to get 17 debuts in the first team and saw some young players really kick on and develop their careers. We worked with some really great staff as well, with really great youth developers.”

After three and a half years in east London, Martin was offered the chance to become Technical Director again at Stoke City, who had been relegated from the top flight and looking to put a strategy in place to help them push for promotion.

“When you go into a club, it's new and there's always challenges. Stoke certainly had some challenges and I saw the opportunity to make my mark and put a foundation in place so that the club could move forward again.

“In my first summer we made 18 new signings, so it was a very busy window. When you've got a lot of a lot of players coming in, it's very hard for all of them to hit the ground running, so they needed some time and now some of them are really developing.”

Martin left Stoke earlier this year, and is now biding his time before making his next move.

“I'm a developer of people and so developing young people in an academy is somewhere that I feel really comfortable. I really enjoy seeing young players develop, but also young practitioners and coaches and medical and sports science staff. My next role won't necessarily be as a technical director or sporting director. It could be back in the academy field and developing young people, departments and systems that need to be put in place to optimise the potential of the club and its academy programme.

“In England, I feel we now have one of the best youth development programmes in the world. The facilities and the infrastructure and everything that goes behind running a successful football club are producing some outstanding talent, not just players but some outstanding youth developers and practitioners.

“I've seen so many changes, such as a lot more emphasis around player care and well-being. There's also work around diversity and I've been lucky to be involved with the Premier League on some action groups to help to increase diversity in the workforce.

“It's really valuable because it clubs needs to reflect the diversity of the players and the fans and that's been an imbalance. It’s really empowering to have such a pivotal role in inspiring our young people and our young players.”

With the game growing for men and women from grassroots to elite level, Martin believes football is a great career for those passionate about working in elite sport.

He added: “There's some great opportunities for support staff at the academies and first teams have also really grown. From data to nutrition, sports science, recruitment operations, logistics and law, there's so many now skill sets that are required to have an effective football club.

“Any young person that wanted to get into the game and we're just talking here about the men's game. But you've also seen the growth of the women's game that's and how their academies are growing now and the great work the WSL is undertaking so I can only see that space getting bigger.

“Whether you go straight in on a work placement and look to develop your career that way, or go to university and get your degree and the qualifications required to come into a football club, it's all about people working really hard and maximising their potential.”

Martin also sees the evolving world of football as a good thing and an opportunity to learn from different viewpoints.

He added: ““The Academy director role and the sporting director roles are constantly evolving. I can see them getting bigger because of the expansion of the different departments and because of how much more diverse the game is becoming. In five years time, I think some of the bigger clubs will have an assistant sporting director with a different skill set to complement their colleague.

“You've already started to see that already in the Premier League with how big the game is becoming. Football is a worldwide game so the more we can open up and the more we can learn from different cultures and different environments around the world is going to be really powerful.

“Sharing of knowledge is important. Obviously the Premier League is a really strong brand at the moment and a lot of people want to come to England to work here. But I also see some great opportunities all around the world where leagues and clubs are doing some unbelievable work. I see some really interesting opportunities going forward.”

[bommagoni]

Histone Deacetylase Inhibitors Market Share, Size, Industry Data

[medicomunicare]

Double-edge swords or unrecognized "factotums"? Reactive electrophiles turn off inflammation while enhancing aging

After activation, immune cells engage in metabolic remodeling to support the energy and biosynthetic demands for proliferation and effector functions. Notably, boosted glucose uptake and flux through glycolysis are common metabolic features of different immune cells. In particular, targeted glycolysis has been shown to profoundly affect immune responses, including infections, inflammation, and…

[geekanoids]

Majority Histon Portable DAB Digital Radio Review

[capralogics01]

sheep anti-histone III

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[whats-in-a-sentence]

Stable or heritable DNA methylation and histone modifications have now been linked with specific abiotic stresses (Figure 24.15).

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[hoiist]

My rook Histon in high def because my machine cant run it and its so upsetting i cant see him in all his amazing glory all the time

[tenth-sentence]

Chromatin immunoprecipitation of DNA cross-linked to modified histones coupled with with modern sequencing technologies, has opened the door to genome-wide analyses of changes in the epigenome.

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[medicomunicare]

Breast cancER using rogue codes: would you BET epigenome is the key for its defeat?

Breast cancER using rogue codes: would you BET epigenome is the key for its defeat?

Luminal-A breast cancer responds well to estrogen receptor alpha (ERα) antagonist drugs, the best known of which is tamoxifen. Through this protein, estrogen drives malignant cell replication that leads to tumor expansion. Not all breast cancers are, however, positive for the presence of ER-alpha. Some subtypes do not express it at all and often this also happens for progesterone receptors…

[humancelltournament]

Human Cell Tournament Round 1

Propaganda!

A killer T cell is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response and is often produced by cancer cells, viruses, bacteria or intracellular signals. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell.

In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.