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Histones

The DNA molecule of individual human chromosomes ranges from 1.7 to 8.5 cm in length when uncoiled. The information stored in DNA is organized, replicated and read by a variety of DNA binding proteins. These fall into two categories:

Structural proteins or Packaging Proteins- These are non -specifically binding proteins. These are bound to DNA along most of its length and help to package it without preventing the access of DNA binding proteins.

Nucleosome Packing Proteins

Histones are the main structural proteins found in eukaryotic cells. Albrecht Kossel (1884) discovered Histones. These are low molecular weight proteins with high proportion of positively charged amino acids (basic amino acids arginine and lysine). The positive charge helps histones to bind to DNA and play a crucial part in packing long DNA molecules.

Types of Histones:

There are five different types of histones that fall into two categories-

1. Nucleosomal Histones- These are small proteins responsible for coiling DNA into nucleosome. These are H2A, H2B, H3 and H4. These are called Core histones. Each of them is formed of about 102-135 amino acids. These form the inner core of nucleosome. Nucleosomal histones are very similar in different species (i.e. these have not changed during evolution). These are present in equimolar amounts; two of each type being presents every 200 base pairs thus forming a histone octamer or core particle.

2. H1 histones- These are large (about 200 amino acids) and are tissue specific. They are present once per 200 base pair. These are loosely asspciated with DNA. H1 histones are responsible for packing of nucleosomes into 30nm fibre. There is also associated H5 histone. Both H1 and H5 histones are called as Likner Histones.

Functions of Histones:

Histones in Eukaryottes serve two functions:-

1. These either serves as structural elements and help in coiling and packing of long DNA molecules.

2. These cover or repress specific segment of DNA, so that they are unable to transcribe. Their transcription is possible only by dissolution of histones in response to certain molecular signals.

Between Histones and DNA following types of interactions are reported:

� There is accumulation of positive charge at the point of interaction of DNA�s negatively charged phosphate groups and alpha helices of H2B, H3, and H4 helix dipoles.

� DNA backbone the and the amide group on the main chain of histone proteins form Hydrogen bonds.

� Histones and deoxyribose sugars on DNA show non-polar interactions

� Basic amino acids (especially lysine and arginine) side chains and phosphate oxygens on DNA form Salt bridges and hydrogen bonds

� Into two minor grooves of DNA molecule, there is an insertion of Non-specific minor groove of the H3 and H2B N-terminal tails.

List of Histone Proteins found in human:

Super family

Family

Subfamily

Members

Linker

H1

H1F

H1F0, H1FNT, H1FOO, H1FX

H1H1

HIST1H1A, HIST1H1B, HIST1H1C, HIST1H1D, HIST1H1E, HIST1H1T

Core

H2A

H2AF

H2AFB1, H2AFB2, H2AFB3, H2AFJ, H2AFV, H2AFX, H2AFY, H2AFY2, H2AFZ

H2A1

HIST1H2AA, HIST1H2AB, HIST1H2AC, HIST1H2AD, HIST1H2AE, HIST1H2AG, HIST1H2AI, HIST1H2AJ, HIST1H2AK, HIST1H2AL, HIST1H2AM

H2A2

HIST2H2AA3, HIST2H2AC

H2B

H2BF

H2BFM, H2BFO, H2BFS, H2BFWT

H2B1

HIST1H2BA, HIST1H2BB, HIST1H2BC, HIST1H2BD, HIST1H2BE, HIST1H2BF, HIST1H2BG, HIST1H2BH, HIST1H2BI, HIST1H2BJ, HIST1H2BK, HIST1H2BL, HIST1H2BM, HIST1H2BN, HIST1H2BO

H2B2

HIST2H2BE

H3

H3A1

HIST1H3A, HIST1H3B, HIST1H3C, HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J

H3A2

HIST2H3C

H3A3

HIST3H3

H4

H41

HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4G, HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L

H44

HIST4H4