CAF-1 is essential for heterochromatin organization in pluripotent embryonic cells.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Embryonic Stem Cells/*physiology ; Heterochromatin/*metabolism ; Pluripotent Stem Cells/*physiology ; Proteins/*genetics ; Proteins/*physiology; Animals ; Blastocyst/physiology ; Embryonic Development ; Epigenesis, Genetic ; Exons ; Exoribonucleases ; Female ; Gene Targeting ; Male ; Mice ; Mice, Inbred C57BL ; Repressor Proteins ; Ribonucleases

During mammalian development, chromatin dynamics and epigenetic marking are important for genome reprogramming. Recent data suggest an important role for the chromatin assembly machinery in this process. To analyze the role of chromatin assembly factor 1 (CAF-1) during pre-implantation development, we generated a mouse line carrying a targeted mutation in the gene encoding its large subunit, p150CAF-1. Loss of p150CAF-1 in homozygous mutants leads to developmental arrest at the 16-cell stage. Absence of p150CAF-1 in these embryos results in severe alterations in the nuclear organization of constitutive heterochromatin. We provide evidence that in wild-type embryos, heterochromatin domains are extensively reorganized between the two-cell and blastocyst stages. In p150CAF-1 mutant 16-cell stage embryos, the altered organization of heterochromatin displays similarities to the structure of heterochromatin in two- to four-cell stage wild-type embryos, suggesting that CAF-1 is required for the maturation of heterochromatin during preimplantation development. In embryonic stem cells, depletion of p150CAF-1 using RNA interference results in the mislocalization, loss of clustering, and decondensation of pericentric heterochromatin domains. Furthermore, loss of CAF-1 in these cells results in the alteration of epigenetic histone methylation marks at the level of pericentric heterochromatin. These alterations of heterochromatin are not found in p150CAF-1-depleted mouse embryonic fibroblasts, which are cells that are already lineage committed, suggesting that CAF-1 is specifically required for heterochromatin organization in pluripotent embryonic cells. Our findings underline the role of the chromatin assembly machinery in controlling the spatial organization and epigenetic marking of the genome in early embryos and embryonic stem cells.
Competing Interests: Competing interests. The authors have declared that no competing interests exist.

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0 (Heterochromatin)
0 (Proteins)
0 (Repressor Proteins)
EC 3.1.- (Cnot7 protein, mouse)
EC 3.1.- (Exoribonucleases)
EC 3.1.- (Ribonucleases)

Date Created: 20061107 Date Completed: 20061213 Latest Revision: 20201209

20250114

PMC1630711

10.1371/journal.pgen.0020181

17083276