The Best Things Come in Small Packages...Except for Full-Grown Bison, Which Require an Awesomely Big Package 

You know when your room gets messy, and you finally decide (that is, your mom yells at you) to clean it by putting books on the shelf, arranging papers into folders, and clearing out the dead longshoreman whom your friends promised never to talk about? After that point, doesn't your room seem way more spacious than when you had all that junk strewn around the place?

The cell also likes to keep things tidy, ordered, and longshoreman-free. It packs DNA so that it does not take up too much space. If you were to stretch out all of the DNA in your body end-to-end, it would be approximately 1.2 × 10¹⁰ miles, which is about 70 trips to the Sun and back. Due to pending litigation, Shmoop can no longer encourage construction of DNA bridges to the Sun.

Packed Like Sardines

The double helix of DNA is highly negatively charged due to all the negatively charged phosphates in the backbone. All that negative charge must be counterbalanced by a positive charge, and the cell makes proteins called histones that bind DNA and aid in DNA's packaging. Histones are positively charged proteins that wrap up DNA through interactions between their positive charges and the negative charges of DNA. Double-stranded DNA loops around 8 histones twice, forming the nucleosome, which is the building block of chromatin packaging.



DNA can be further packaged by forming coils of nucleosomes, called chromatin fibers. These fibers are condensed into chromosomes during mitosis, or the process of cell division. However, packaging of chromatin into chromosomes that we are most familiar with occurs only during a few stages of mitosis. Most of the time, DNA is loosely packaged.

Histones: DNA Tupperware^TM  

Histones are positively charged proteins that facilitate the packing of DNA into condensed chromatin fibers. They are basically the Tupperware^TM of DNA packaging, and they come in many kitchen-friendly colors. Histones have many arginine and lysine amino acids that easily bind to the negatively charged DNA, based on Paula Abdul's principle that opposites attract. Just kidding on that last part. DNA is highly negatively charged because of the phosphate group of each nucleotide is negatively charged.



Histones are divided into two groups: 

• Core histones
   
• Linker histones
   

Core histones are H2A, H2B, H3, and H4, where two H3/H4 dimers (H3 and H4 hooked together) and two H2A/H2B dimers (these two hooked together) form the octamer (all eight of these guys together). Linker histone H1 basically locks the DNA in place onto the nucleosome and can be removed for transcription while linker histone H5 is a variant of H1 predominantly used in birds.



Is that confusing? Well, it gets worse. H1, H2A, H2B, H3, H4, and H5 are all names that define families of proteins. Individual histone proteins are specific for certain types of DNA or certain cell types. Just as H5 is the avian version of H1, there are individual histone proteins that package certain regions of DNA, or package DNA in specific tissue types. Just like you would not put a giant pot of chili in small Tupperware containers (or maybe you would…we try not to judge, but seriously?), specific histones are important for specific parts of DNA. 

One important aspect of histones is that they can be changed to alter how much packing the DNA is capable of. There are several modifications that affect how well DNA is packaged. The three major types of modifications can be seen in the following table.
  

Modification	Modification Structure (R = chemical functional group)	Charge	Effect
Methylation	R-CH3	Neutral	Increases packing
Acetylation	R-COCH3	Negative	Decreases packing
Phosphorylation	R-PO4	Negative	Decreases packing

 
Normally, histones are positively charged molecules, and the addition of methyl groups (methylation) makes them more hydrophobic (water-hating). Hydrophobic molecules tend to stick together, and increasing histone methylation will cause the histones to pack even more tightly than usual.  

Acetylation (adding an acetyl group) and phosphorylation (adding a phosphate group) make the histones more negatively charged because acetyl and phosphoryl groups are negative. They are "glass is half empty" molecules. By making histones more negatively charged, their grip on DNA will be much looser because DNA is also negatively charged. Similar charges (negative and negative) repel one another. 

Lockup: DNA Edition 

One of the perks of packaging DNA is that you can separate it into things you use a lot and things you do not. Unless you are a maniacal hoarder, every fall, you put away your summer clothes for things more winter-appropriate. In the same way, certain parts of DNA are only important for certain times. However, some things you need year-round, like shoes, so there is no point in putting those things away. The cell does the same thing with DNA. 

Regions that are necessary for making proteins and are important for the cell are loosely packed and called euchromatin. By having a loose packing of DNA in euchromatin, proteins involved in transcription can easily get in and make RNA (see Genes to Proteins section for more detail). On the other hand, some regions of DNA you do not need except for special occasions, like that velvet suit you have that you never wear. These regions are called heterochromatin and are tightly packed through DNA as well as through good ol' histone methylation. 



Enzymes that add acetyl groups to histones are called histone acetyltransferases (HATs) while those that remove acetyl groups are called histone deacetylases (HDACs). Enzymes that add methyl groups are called histone methyltransferases (HMTs). Activity of these enzymes affects whether or not regions of DNA are tightly packed, and unable to transcribe, or are loosely packed and therefore, highly transcribed.  

Histone methylation is a tricky concept, though, because usually, histone methylation goes along with methylation of cytosines in DNA, called DNA methylation. Together, these processes create regions of DNA that cannot be transcribed. However, sometimes, methylation of positively charged amino acids in histones promotes transcriptional activation, but only when DNA is not methylated. The methylation of DNA and modifications of histones that affect transcription are the focus of study called epigenetics. 

When the cell is undergoing the process of mitosis, chromatin packing is important, and this packing is done by packing DNA into condensed chromatin fibers to the point where they are the recognized chromosomes that we know and love…or "really like," if you are unprepared to make that kind of commitment. These chromosomes divide into daughter cells, and after mitosis is complete, the DNA is unpacked so transcription can occur again. Therefore, we can think of mitosis like a big DNA moving day. The packing starts with HDACs and HMTs tightening the packaging, and once mitosis is completed, HATs and phosphoryltransferases (HPTs) reduce the packaging.

Brain Snack

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