Review Article | Published:

Old cogs, new tricks: the evolution of gene expression in a chromatin context

Nature Reviews Geneticsvolume 20pages283297 (2019) | Download Citation


Sophisticated gene-regulatory mechanisms probably evolved in prokaryotes billions of years before the emergence of modern eukaryotes, which inherited the same basic enzymatic machineries. However, the epigenomic landscapes of eukaryotes are dominated by nucleosomes, which have acquired roles in genome packaging, mitotic condensation and silencing parasitic genomic elements. Although the molecular mechanisms by which nucleosomes are displaced and modified have been described, just how transcription factors, histone variants and modifications and chromatin regulators act on nucleosomes to regulate transcription is the subject of considerable ongoing study. We explore the extent to which these transcriptional regulatory components function in the context of the evolutionarily ancient role of chromatin as a barrier to processes acting on DNA and how chromatin proteins have diversified to carry out evolutionarily recent functions that accompanied the emergence of differentiation and development in multicellular eukaryotes.

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The authors thank S. Brahma, K. Ahmad and the reviewers for helpful suggestions on the manuscript.

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Nature Reviews Genetics thanks K. Struhl and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    • Paul B. Talbert
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Histone fold domain

(HFD). A protein dimerization domain of three helices separated by two loops that is characteristic of archaeal and core eukaryotic histones, TATA-binding protein-associated factors and some other proteins.

Four-helix bundles

Structures formed by two helices of each of two histones that enable dimers to assemble into more complex structures.


Anaerobic cells typically with two pairs of basal bodies with one posterior and three anterior flagella. Metamonads include the diplomonad Giardia intestinalis and the parabasalid Trichomonas vaginalis, among others, and may represent one of the earliest branches of the eukaryotic phylogenetic tree.


Flagellates that have a dense mass of DNA called a kinetoplast, which contains many copies of the mitochondrial genome. Kinetoplastids include Bodonids and trypanosomes and are thought to represent an early branch of the eukaryotic phylogenetic tree.

SET domain

A protein domain generally associated with protein lysine methyltransferase activity.

Last eukaryotic common ancestor

(LECA). The most recent cell that was ancestral to all extant eukaryotes, inferred to be a complex nucleated cell with an endomembrane system, a cytoskeleton, a mitochondrion, and linear chromosomes that were packaged in nucleosomes and underwent mitosis and meiosis.

First eukaryotic common ancestor

(FECA). A hypothetical first cell that was ancestral to all eukaryotes and distinct from bacteria and archaea, variously conceived as an urkaryote or a chimeric organism composed of host and endosymbiont.


A hypothetical cell ancestral to the eukaryotic cytoplasm with distinct features of the translational apparatus that distinguish it from archaea and bacteria and that arose independently from the last universal cellular ancestor.


A cell or organism living inside another cell or organism.


A cell in any stage of eukaryotic evolution between the first eukaryotic common ancestor to the last eukaryotic common ancestor.

General transcription factors

The factors that together with RNA polymerase II make up the pre-initiation complex for transcription.

Nucleocytoplasmic large DNA viruses

(NCLDVs). A diverse monophyletic group of fairly large, complex DNA viruses, including giant viruses such as the Marseilleviridae as well as other more modestly sized viruses.


Histone H3 variant specific to centromeric nucleosomes, examples of which include mammalian CENP-A and budding yeast Cse4.


The process of evolving from the first eukaryotic common ancestor to the last eukaryotic common ancestor.


Archaeal histone polymers of variable length that wrap DNA.

Monophyletic group

A group of genes, proteins or organisms that includes all the descendants of a single common ancestor and excludes others.


A proteinaceous structure that encloses a viral genome for protection and dispersion.

Winged helix domain

A protein domain with combined specific and nonspecific DNA-binding affinity characterized by a helix–turn–helix motif flanked by β-sheets on one or both sides.


The degree of torsion or supercoiling in a DNA molecule.


Writhed loops resulting from supercoiling.

Enhancer RNAs

(eRNAs). Non-coding RNAs transcribed from enhancers.

Topologically associating domains

(TADs). Regions of the genome that interact with themselves in 3D nuclear space more often than regions outside the TAD.

+1 Nucleosome

A highly conserved nucleosome positioned downstream of the nucleosome-depleted region, which acts as a barrier to transcription elongation by RNA polymerase.

Pioneer factors

Transcription factors that can bind to nucleosome-occluded DNA and promote accessibility to transcription, often at an early step in a developmental pathway.

CpG islands

Regions of more than 200 bp near many mammalian promoters that are enriched for CG dinucleotides.


Cells of the pituitary gland that secrete luteinizing hormone and follicle-stimulating hormone.

Homotypic nucleosomes

Nucleosomes in which both members of any particular histone family are the same histone variant.

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