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IndranilSinha - 29 May 2009
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Histone Overview (Figure from Biology: Concepts and Connections by Campell, Mitchell, and Reece. Text from Introduction to Cell and Molecular Biology by Stephen L. Wolfe)
Histones combine with DNA to form nucleosomes, the fundamental structural units of chromatin. Nucleosomes pack DNA in a stable coiled form in eukaryotic nuclei. The total DNA complement of the nucleus, with associated histone and non-histone proteins, is broken into individual lengths; these are the chromosomes.
The coiling of DNA around nucleosomes and the further winding of nucleosomes into chromatin fibers greatly compact the DNA of the eukaryotic nuclei. Winding the DNA into nucleosomes and chromatin fibers is estimated to shorten its length by at least a factor of 10,000.
Because packing of nucleosomes in chromatin fibers probably prevents access to DNA by the enzymes of transcription and replication, the fibers probably unwind for these activities to take place. The increased sensitivity of active chromatin to endonuclease digestion indicates that even nucleosomes probably unfold or dissassemble from DNA as it enters transcription or replication. All of this points to the conclusion that chromatin in intact nuclei is highly dynamic, with different folding conformations that reflect its activity. [The figure on the left shows DNA structure from unpacked double helix (top) to fully compacted chromosome (bottom)]
( www.unc.edu/depts/marzluff/histone.html)
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The overall structural organisation of the nucleosome
Each of the core histones contains an N-terminal tail, that can be modified in several ways.
Histone methylation is the modification of certain amino acids in a histone protein by the addition of one, two, or three methyl groups.
This modification alters the properties of the nucleosome and affects its interactions with other proteins.
Histone methylation is generally associated with transcriptional repression.
However, methylation of some lysine and arginine residues of histones results in transcriptional activation. Examples include methylation of lysine 4 of histone 3 (
H3K4? ), and lysine 36 histone 36 (
H3K36? ).
More refferences:
The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation.
Yoh SM, Lucas JS, Jones KA. Genes Dev. 2008 Dec 15;22(24):3422-34. PMID: 19141475 [PubMed - indexed for MEDLINE]
Histone methyltransferase protein SETD2 interacts with p53 and selectively regulates its downstream genes.
Xie P, Tian C, An L, Nie J, Lu K, Xing G, Zhang L, He F. Cell Signal. 2008 Sep;20(9):1671-8. Epub 2008 Jun 27. PMID: 18585004 [PubMed - indexed for MEDLINE]
Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation.
Edmunds JW, Mahadevan LC, Clayton AL. EMBO J. 2008 Jan 23;27(2):406-20. Epub 2007 Dec 20. PMID: 18157086 [PubMed - indexed for MEDLINE]
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