Histone H3.3 regulates mitotic progression in mouse embryonic fibroblasts.
H3.3 is a histone variant that marks transcription start sites as well as telomeres and heterochromatic sites on the genome. The presence of H3.3 is thought to positively correlate with the transcriptional status of its target genes. Using a conditional genetic strategy against H3.3B, combined with short hairpin RNAs against H3.3A, we essentially depleted all H3.3 gene expression in mouse embryonic fibroblasts. Following nearly complete loss of H3.3 in the cells, our transcriptomic analyses show very little impact on global gene expression or on the localization of histone variant H2A.Z. Instead, fibroblasts displayed slower cell growth and an increase in cell death, coincident with large-scale chromosome misalignment in mitosis and large polylobed or micronuclei in interphase cells. Thus, we conclude that H3.3 may have an important under-explored additional role in chromosome segregation, nuclear structure, and the maintenance of genome integrity.
a Université de Grenoble Alpes, Institute for Advanced Biosciences, INSERM U1209/CNRS 5309, 38700 La Tronche, France.|b Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, 06800 Ankara, Turkey.
Aysegul
A
Ors
c Université de Strasbourg, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, Equipe labélisée Ligue contre le Cancer, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France.
Christophe
C
Papin
d Université de Grenoble Alpes, Team GREPI, Etablissement Français du Sang, EA 7408, BP35, 38701 La Tronche, France.
Bertrand
B
Favier
a Université de Grenoble Alpes, Institute for Advanced Biosciences, INSERM U1209/CNRS 5309, 38700 La Tronche, France.
Yohan
Y
Roulland
a Université de Grenoble Alpes, Institute for Advanced Biosciences, INSERM U1209/CNRS 5309, 38700 La Tronche, France.
Defne
D
Dalkara
e Izmir Biomedicine and Genome Center, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
Mehmet
M
Ozturk
c Université de Strasbourg, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, Equipe labélisée Ligue contre le Cancer, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France.
Ali
A
Hamiche
a Université de Grenoble Alpes, Institute for Advanced Biosciences, INSERM U1209/CNRS 5309, 38700 La Tronche, France.
Stefan
S
Dimitrov
f Université de Lyon, Institut de Génomique Fonctionnelle de Lyon, CNRS UMR 5242, Ecole normale supérieur de Lyon, Université Claude Bernard Lyon 1, 46 Allée d'Italie, F-69364 Lyon, France.
Kiran
K
Padmanabhan
D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D020090:Chromosome Segregation; D005347:Fibroblasts / Q000378:metabolism*; D016678:Genome; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000235:genetics*
D006657:Histones
H3.3; RNA-seq; fibroblastes embryonnaires de souris; mitose; mitosis; mouse embryonic fibroblasts; transcription