Editing Histone (section)

== History ==
Histones were discovered in 1884 by [[Albrecht Kossel]].<ref>{{cite book | vauthors = Luck JM | date = 1965 | chapter = Histone Chemistry: the Pioneers | title = The Nucleohistones |editor1-link=James F. Bonner |editor2-link=Paul Ts'o | veditors = Bonner J, Ts'o P | publisher = Holden-Day, Inc | location = San Francisco, London, and Amsterdam }}</ref> The word "histone" dates from the late 19th century and is derived from the German word ''"Histon"'', a word itself of uncertain origin, perhaps from Ancient Greek ''ἵστημι'' (hístēmi, “make stand”) or ''ἱστός'' (histós, “loom”).

In the early 1960s, before the types of histones were known and before histones were known to be highly conserved across taxonomically diverse organisms, [[James F. Bonner]] and his collaborators began a study of these proteins that were known to be tightly associated with the DNA in the nucleus of higher organisms.<ref name="James Bonner 1994">{{cite journal | vauthors = Bonner J | date = 1994 | title = Chapters from my life | journal = Annual Review of Plant Physiology and Plant Molecular Biology | volume = 45 | pages = 1–23 | doi = 10.1146/annurev.pp.45.060194.000245 | doi-access = free }}</ref> Bonner and his postdoctoral fellow [[Ru Chih C Huang|Ru Chih C. Huang]] showed that isolated chromatin would not support RNA transcription in the test tube, but if the histones were extracted from the chromatin, RNA could be transcribed from the remaining DNA.<ref>{{cite journal | vauthors = Huang RC, Bonner J | title = Histone, a suppressor of chromosomal RNA synthesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 48 | issue = 7 | pages = 1216–22 | date = July 1962 | pmid = 14036409 | pmc = 220935 | doi = 10.1073/pnas.48.7.1216 | bibcode = 1962PNAS...48.1216H | doi-access = free }}</ref> Their paper became a citation classic.<ref>{{cite journal | title = Huang R C & Bonner J. Histone, a suppressor of chromosomal RNA synthesis. Proc. Nat. Acad. Sci. US 48:1216-22, 1962. | url = http://garfield.library.upenn.edu/classics1978/A1978EP01300002.pdf | journal = Citation Classics | date = 20 March 1978 | issue = 12 | pages = 79 }}</ref>  Paul T'so and James Bonner had called together a World Congress on Histone Chemistry and Biology in 1964, in which it became clear that there was no consensus on the number of kinds of histone and that no one knew how they would compare when isolated from different organisms.<ref name="Bonner">James Bonner and Paul T'so (1965) ''The Nucleohistones''. Holden-Day Inc, San Francisco, London, Amsterdam.</ref><ref name="James Bonner 1994"/>  Bonner and his collaborators then developed methods to separate each type of histone, purified individual histones, compared amino acid compositions in the same histone from different organisms, and compared amino acid sequences  of the same histone from different organisms in collaboration with [[Emil L. Smith|Emil Smith]] from UCLA.<ref name="DeLange-1969">{{cite journal | vauthors = DeLange RJ, Fambrough DM, Smith EL, Bonner J | title = Calf and pea histone IV. 3. Complete amino acid sequence of pea seedling histone IV; comparison with the homologous calf thymus histone | journal = The Journal of Biological Chemistry | volume = 244 | issue = 20 | pages = 5669–79 | date = October 1969 | pmid = 5388597 | doi = 10.1016/S0021-9258(18)63612-9| doi-access = free }}</ref> For example, they found Histone IV sequence to be highly conserved between peas and calf thymus.<ref name="DeLange-1969" />  However, their work on the biochemical characteristics of individual histones did not reveal how the histones interacted with each other or with DNA to which they were tightly bound.<ref name="Bonner"/>

Also in the 1960s, Vincent Allfrey and [[Alfred Mirsky]] had suggested, based on their analyses of histones, that acetylation and methylation of histones could provide a transcriptional control mechanism, but did not have available the kind of detailed analysis that later investigators were able to conduct to show how such regulation could be gene-specific.<ref>{{cite journal | vauthors = Allfrey VG, Faulkner R, Mirsky AE | title = Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 51 | issue = 5 | pages = 786–94 | date = May 1964 | pmid = 14172992 | pmc = 300163 | doi = 10.1073/pnas.51.5.786 | bibcode = 1964PNAS...51..786A | doi-access = free }}</ref>  Until the early 1990s, histones were dismissed by most as inert packing material for eukaryotic nuclear DNA, a view based in part on the models of [[Mark Ptashne]] and others, who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, as is the case in bacteria.

During the 1980s, Yahli Lorch and [[Roger D. Kornberg|Roger Kornberg]]<ref>{{cite journal |vauthors=Lorch Y, LaPointe JW, Kornberg RD |date=April 1987 |title=Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones |url=https://pubmed.ncbi.nlm.nih.gov/3568125/ |journal=Cell |volume=49 |issue=2 |pages=203–10 |doi=10.1016/0092-8674(87)90561-7 |pmid=3568125 |s2cid=21270171|doi-access=free }}</ref> showed that a nucleosome on a core promoter prevents the initiation of transcription in vitro, and [[Michael Grunstein]]<ref>{{cite journal |vauthors=Kayne PS, Kim UJ, Han M, Mullen JR, Yoshizaki F, Grunstein M |date=October 1988 |title=Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast |url=https://www.cell.com/cell/pdf/0092-8674(88)90006-2.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2F0092867488900062%3Fshowall%3Dtrue |journal=Cell |volume=55 |issue=1 |pages=27–39 |doi=10.1016/0092-8674(88)90006-2 |pmid=3048701 |s2cid=7994350}}</ref> demonstrated that histones repress transcription in vivo, leading to the idea of the nucleosome as a general gene repressor.  Relief from repression is believed to involve both histone modification and the action of chromatin-remodeling complexes.  Vincent Allfrey and Alfred Mirsky had earlier proposed a role of histone modification in transcriptional activation,<ref>{{cite journal | vauthors = Pogo BG, Allfrey VG, Mirsky AE | title = RNA synthesis and histone acetylation during the course of gene activation in lymphocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 55 | issue = 4 | pages = 805–12 | date = April 1966 | pmid = 5219687 | pmc = 224233 | doi = 10.1073/pnas.55.4.805 | bibcode = 1966PNAS...55..805P | doi-access = free }}</ref> regarded as a molecular manifestation of epigenetics. Michael Grunstein<ref>{{cite journal |vauthors=Durrin LK, Mann RK, Kayne PS, Grunstein M |date=June 1991 |title=Yeast histone H4 N-terminal sequence is required for promoter activation in vivo |url=https://www.cell.com/cell/pdf/0092-8674(91)90554-C.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2F009286749190554C%3Fshowall%3Dtrue |journal=Cell |volume=65 |issue=6 |pages=1023–31 |doi=10.1016/0092-8674(91)90554-c |pmid=2044150 |s2cid=28169631}}</ref> and David Allis<ref>{{cite journal | vauthors = Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD | title = Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation | journal = Cell | volume = 84 | issue = 6 | pages = 843–51 | date = March 1996 | pmid = 8601308 | doi = 10.1016/s0092-8674(00)81063-6 | doi-access = free }}</ref> found support for this proposal, in the importance of histone acetylation for transcription in yeast and the activity of the transcriptional activator Gcn5 as a histone acetyltransferase.

The discovery of the H5 histone appears to date back to the 1970s,<ref>{{cite journal | vauthors = Aviles FJ, Chapman GE, Kneale GG, Crane-Robinson C, Bradbury EM | title = The conformation of histone H5. Isolation and characterisation of the globular segment | journal = European Journal of Biochemistry | volume = 88 | issue = 2 | pages = 363–71 | date = August 1978 | pmid = 689022 | doi = 10.1111/j.1432-1033.1978.tb12457.x | doi-access = free }}</ref> and it is now considered an [[isoform]] of [[Histone H1]].<ref name="Nelson&Cox"/><ref name="HistoneDB"/><ref name="Bhasin_2006"/><ref name="HartlFreilfelder&Snyder"/>