A developmental requirement for HIRA-dependent H3.3 deposition revealed at gastrulation in Xenopus.
Discovering how histone variants that mark distinct chromatin regions affect a developmental program is a major challenge in the epigenetics field. To assess the importance of the H3.3 histone variant and its dedicated histone chaperone HIRA, we used an established developmental model, Xenopus laevis. After the early rapid divisions exploiting a large maternal pool of both replicative H3.2 and replacement H3.3, H3.3 transcripts show a distinct peak of expression at gastrulation. Depletion of both H3.2 and H3.3 leads to an early gastrulation arrest. However, with only H3.3 depletion, defects occur at late gastrulation, impairing further development. Providing exogenous H3.3 mRNAs, but not replicative H3.2 mRNAs, rescues these defects. Notably, downregulation of the H3.3 histone chaperone HIRA similarly impairs late gastrulation, and we find a global defect in H3.3 incorporation into chromatin comparable to H3.3 depletion. We discuss how specific HIRA-dependent H3.3 deposition is required for chromatin dynamics during gastrulation.
Institut Curie, Centre de Recherche, Paris F-75248 France.
Emmanuelle
E
Szenker
Nicolas
N
Lacoste
Geneviève
G
Almouzni
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D054262:Gastrulation / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism*
D015415:Biomarkers; D002843:Chromatin; D056488:Histone Chaperones; D006657:Histones; D060172:Morpholinos; D020825:T-Box Domain Proteins; C116765:TBXT protein, Xenopus; D029867:Xenopus Proteins