Editing Histone (section)

== Histone Chaperones ==
Histone [[chaperones (biology)]] are specialized proteins that assist in the proper handling, transport, and assembly of histones, preventing their aggregation and ensuring their appropriate deposition onto DNA. These proteins play a crucial role in regulating [[nucleosome]] assembly and disassembly, influencing transcriptional activity, DNA replication, and repair. Unlike enzymatic [[chromatin remodeling]], histone chaperones function by binding histones in a regulated manner, modulating chromatin structure without direct catalytic activity.<ref name="Gurard-Levin_2014">{{cite journal | vauthors = Gurard-Levin ZA, Quivy JP, Almouzni G | title = Histone chaperones: assisting histone traffic and nucleosome dynamics | journal = Annual Review of Biochemistry | volume = 83 | issue = 1 | pages = 487–517 | date = 2014-06-02 | pmid = 24905786 | doi = 10.1146/annurev-biochem-060713-035536 }}</ref> 

One key function of histone chaperones is maintaining a reservoir of histones, regulating their supply to ensure proper chromatin formation. During DNA replication and [[transcription (biology)]], histone chaperones such as ASF1 and FACT facilitate nucleosome reassembly, ensuring the preservation of histone modifications that define cellular identity. Moreover, histone chaperones contribute to [[nucleosome]] disassembly in response to cellular stress or DNA damage, thereby allowing access to repair machinery.

Histone chaperones also participate in the selective deposition of histone variants, which are functionally distinct from [[canonical]] histones. For example, [[HIRA]] is a chaperone that specifically deposits the histone variant H3.3, a marker of active chromatin regions. Similarly, [[CAF-1]] is responsible for incorporating H3.1 and H3.2 into newly replicated DNA, highlighting the functional specialization within chaperone networks.<ref name="Venkatesh_2015">{{cite journal | vauthors = Venkatesh S, Workman JL | title = Histone exchange, chromatin structure and the regulation of transcription | journal = Nature Reviews. Molecular Cell Biology | volume = 16 | issue = 3 | pages = 178–189 | date = March 2015 | pmid = 25650798 | doi = 10.1038/nrm3941 }}</ref>

Given their critical roles, misregulation of histone chaperones has been implicated in diseases such as cancer. Aberrant chaperone activity can lead to improper histone deposition, [[genome instability]], and altered gene expression, contributing to [[tumorigenesis]]. Current research is exploring histone chaperones as potential therapeutic targets, particularly in cancers characterized by disrupted chromatin landscapes.<ref name="Gurard-Levin_2014" />

=== Chaperone Networks ===
The coordinated action of multiple histone chaperones forms an intricate network responsible for histone transport, [[Chromatin assembly factor 1]], and [[genome]] maintenance. Chaperone networks facilitate the transport of histones which are synthesized in the [[cytoplasm]] and must be escorted to the [[cell nucleus]]. This network ensures histones are deposited at the appropriate genomic locations, maintaining [[chromatin]] integrity and function.<ref>{{cite journal | vauthors = Li Z, Zhang Z | title = Histone chaperones: A multinodal highway network inside the cell | journal = Molecular Cell | volume = 83 | issue = 7 | pages = 1024–1026 | date = April 2023 | pmid = 37028413 | pmc = 10332477 | doi = 10.1016/j.molcel.2023.03.004 }}</ref>

Histone chaperones play a crucial role in responding to DNA damage by regulating chromatin accessibility. For example, in response to [[double strand breaks]], chaperones such as FACT and ASF1 help disassemble nucleosomes at damage sites, allowing repair factors to access the lesion. Once repair is completed, these chaperones facilitate the reassembly of [[Nucleosome|nucleosomes]], restoring chromatin structure and ensuring epigenetic information is maintained.<ref>{{cite journal | vauthors = Polo SE | title = Reshaping chromatin after DNA damage: the choreography of histone proteins | journal = Journal of Molecular Biology | volume = 427 | issue = 3 | pages = 626–636 | date = February 2015 | pmid = 24887097 | pmc = 5111727 | doi = 10.1016/j.jmb.2014.05.025 }}</ref> 

In addition to their role in genome stability, histone chaperones contribute to [[epigenetic inheritance]]. During cell division, chromatin states must be faithfully propagated to daughter cells. Chaperones help distribute parental histones onto newly synthesized DNA strands, preserving histone modifications and ensuring continuity of cellular identity. Disruptions in these processes can lead to epigenetic abnormalities associated with developmental disorders.<ref>{{cite journal | vauthors = Li Z, Zhang Z | title = Histone chaperones: A multinodal highway network inside the cell | journal = Molecular Cell | volume = 83 | issue = 7 | pages = 1024–1026 | date = April 2023 | pmid = 37028413 | pmc = 10332477 | doi = 10.1016/j.molcel.2023.03.004 }}</ref>