Journal of Molecular Biology
ReviewOPERating ON Chromatin, a Colorful Language where Context Matters
Section snippets
The “histone code hypothesis”: the first 10 years
In 2000, we proposed what has come to be commonly referred to as the “histone code hypothesis,” which, in its original form, posits that “multiple histone modifications, acting in a combinatorial or sequential fashion on one or multiple histone tails, specify unique downstream functions.”15 Parallels to François Jacob's quote from “Evolution and Tinkering” are readily apparent. The same fixed set of amino acids that make up the histone proteins have the potential of being post-translationally
Transcribing the “histone code”: chicken or egg?
Although applicable to a diverse set of cellular processes, the histone code is most commonly considered in the context of transcription regulation. Within this realm, there has been much debate as to whether a putative code formed by combinatorial modifications can formally regulate transcription itself or, rather, if patterns of modifications are generally associated with a particular transcriptional state. On one side is the argument that genes are not necessarily regulated by chromatin
Tinkering the “histone code hypothesis” in years to come
The key question that remains then is perhaps not one of mulling over how to best define the histone code, but rather, what form will the histone code hypothesis take over the years to come? Given the rapidity of chromatin-based research and the prominent role of chromatin in numerous DNA-based processes, research in the years to come is likely to continue along the same fruitful path of discovery that it has witnessed in the past 10 years, demonstrating additional levels of complexity by which
Strict code versus rich language: exciting either way
At the time of inception, it is always difficult to discern how influential a hypothesis will truly be. We have been privileged to witness that François Jacob and Jacques Monod's report on the lac operon in the Journal of Molecular Biology in 1961 has revolutionized our understanding of the basic mechanisms underlying gene regulation. We are also beginning to understand the richness of the histone code hypothesis. When we posited this hypothesis, now 10 years ago, we had what in retrospect
Acknowledgements
We thank the many researchers whose studies have help to expand our understanding of both the lac operon and the histone code, and we apologize to those whose work could not be cited here due to space constraints. We also thank Nara Lee, Scott Rothbart, and the members of the Allis laboratory for insightful conversations and comments on the manuscript, and Nara Lee and Stephen Fuchs for assistance with the illustrations contained in this piece.
References (78)
- et al.
Genetic regulatory mechanisms in the synthesis of proteins
J Mol Biol
(1961) Fundamentally different logic of gene regulation in eukaryotes and prokaryotes
Cell
(1999)- et al.
Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome
Cell
(1999) - et al.
Electron microscopic and biochemical evidence that chromatin structure is a repeating unit
Cell
(1975) Chromatin modifications and their function
Cell
(2007)- et al.
Lysine propionylation and butyrylation are novel post-translational modifications in histones
Mol. Cell Proteomics
(2007) - et al.
Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein
Mol. Cell
(2009) - et al.
Phosphotyrosine signaling: evolving a new cellular communication system
Cell
(2010) - et al.
Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark
Mol. Cell
(2007) - et al.
The language of histone crosstalk
Cell
(2010)
What's up and down with histone deacetylation and transcription?
Cell
Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4
Cell
Histone crosstalk between H3S10ph and H4K16ac generates a histone code that mediates transcription elongation
Cell
Characterization of histones and their post-translational modifications by mass spectrometry
Curr. Opin. Chem. Biol.
High throughput characterization of combinatorial histone codes
Mol. Cell. Proteomics.
Influence of combinatorial histone modifications on antibody and effector protein recognition
Curr. Biol.
High-resolution profiling of histone methylations in the human genome
Cell
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Cell
A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation
Mol. Cell.
Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers
Cell
Nucleosome-interacting proteins regulated by DNA and histone methylation
Cell
Acetylation and deacetylation of non-histone proteins
Gene
The emerging field of dynamic lysine methylation of non-histone proteins
Curr. Opin. Genet. Dev.
Evolution and tinkering
Science
[Operon: a group of genes with the expression coordinated by an operator.]
C R Hebd Seances Acad. Sci.
Crystal structure of the nucleosome core particle at 2.8 Å resolution
Nature
Chromatin structure: a repeating unit of histones and DNA
Science
Chromatin disruption and modification
Nucleic Acids Res.
The complex language of chromatin regulation during transcription
Nature
The biology of chromatin remodeling complexes
Annu. Rev. Biochem.
Chromatin remodelling during development
Nature
Histone variants—ancient wrap artists of the epigenome
Nat. Rev. Mol. Cell Biol.
The language of covalent histone modifications
Nature
β-N-Acetylglucosamine (O-GlcNAc) is part of the histone code
Proc. Natl Acad. Sci. USA
The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules
Nat. Struct. Mol. Biol.
How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers
Nat. Struct. Mol. Biol.
Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1
Nat. Struct. Mol. Biol.
PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression
Nature
Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B
Science
Cited by (286)
CRISPR, epigenetics, and cancer
2023, Epigenetic Cancer Therapy, Second EditionA capped Tudor domain within a core subunit of the Sin3L/Rpd3L histone deacetylase complex binds to nucleic acid G-quadruplexes
2022, Journal of Biological ChemistryMetabolic enzymes function as epigenetic modulators: A Trojan Horse for chromatin regulation and gene expression
2021, Pharmacological ResearchArsenic-induced epigenetic changes in cancer development
2021, Seminars in Cancer BiologyTranscriptome and epigenome analysis of engram cells: Next-generation sequencing technologies in memory research
2021, Neuroscience and Biobehavioral Reviews