Chaperoning histones and controlling genome function

Chaperoning histones and controlling genome function

Histone proteins are critical components of chromatin and the incorporation of different histone variants modulates nucleosome stability. Deposition of histones at the right time and the correct place in the genome is tightly controlled by specific histone chaperone complexes. In its last study  , the team of Aline Probst and Christophe Tatout characterized the Arabidopsis ATRX (Alpha Thalassemia-mental Retardation X-linked) homologue. Using reverse genetic approaches along with genome wide analyses Duc et al show that loss of ATRX modulates the cellular balance between canonical H3.1 and its variant H3.3 and leads to reduced H3.3 deposition at set of genes with elevated H3.3 occupancy and high gene expression. This study further elucidates the network of histone chaperones in plants and reveals a specific role for ATRX in histone H3.3 deposition.


This work is published in The Plant Cell (Duc et al., 2017).

Chromatin enables compaction of the DNA within the nucleus and is composed of subunits named nucleosomes. Histones, as essential components of the nucleosome, need to be deposited in a timely- and space-controlled manner to ensure proper DNA organization as well as the setting and maintenance of epigenetic marks including covalent modifications of histone tails and incorporation of specific histone variants. Indeed, canonical histones defined as those assembled during DNA-replication can be replaced by specific histone variants to modulate nucleosome structure and stability. Fine-tuning of histone deposition is therefore critical and is achieved by the so-called histone chaperone complexes, which can specifically deposit canonical histones or their variants. Regarding the model plant Arabidopsis thaliana, the H3.3 variant differs from the canonical H3.1 histone by only four amino acids. Despite these small differences, H3.1 is preferentially enriched at heterochromatic regions, while H3.3 is rather enriched at active genes, promoters and telomeric repeats.

Through a reverse genetic approach along with genome-wide analyses in collaboration with M. Benhamed (Institute of Plant Sciences Paris-Saclay), Aline Probst and Christophe Tatout’s group characterized the Arabidopsis Alpha Thalassemia-mental Retardation X-linked (ATRX) orthologue as a H3.3 chaperone. Contrary to other organisms, Arabidopsis ATRX loss-of-function alleles are viable. However, upon combination with mutants in the histone H3.3 chaperone HIRA (Histone Regulator A), ATRX loss causes lethality, thus strongly suggesting that HIRA and ATRX are involved in complementary histone H3.3 deposition pathways. In atrx mutant plants, H3.1 and H3.3 pools are inversely affected and H3.3 occupancy reduced in a genome-wide manner. Moreover, ATRX modulates gene expression as well as H3.3 deposition for a set of genes with elevated H3.3 occupancy and high gene expression, including the 45S ribosomal DNA (45S rDNA) loci, which are highly enriched in H3.3.

In conclusion, ATRX plays a major role in the maintenance of H3.3 variant occupancy at a genome-wide level at genes and at the 45S rRNA gene loci. Loss of ATRX affects H3.3 histone pools and H3.3 deposition and therefore modulates the H3.1/H3.3 balance in the cell. Moreover, ATRX loss results in altered 45S rRNA variant choice and gene expression changes identifying ATRX as a H3.3 chaperone in plants and revealing the importance of controlled histone deposition in fine-tuning gene expression.



Duc C, Benoit M, Détourné G, Simon L, Poulet A, Jung M, Veluchamy A, Latrasse D, Le Goff S, Cotterell S, Tatout C, Benhamed M, Probst AV. Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression. Plant Cell. 2017 Jul 6. pii: tpc.00877.2016. doi: 10.1105/tpc.16.00877.


Last modified: 04/23/2018