Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.
Bottom Line: In particular, we show that the chromatin remodeller HDAC1-NuRD complex is enriched at nascent DNA.Interestingly, an acute block of HDAC1 in ESCs leads to increased acetylation of histone H3 lysine 9 at nascent DNA together with a concomitant loss of methylation.Consistently, in contrast to what has been described in tumour cell lines, these chromatin marks were found to be stable during cell cycle progression of ESCs.
Affiliation: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden email@example.com.Show MeSH
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Mentions: In addition to the DNA replication cluster, the protein network at nascent DNA in ESCs encompasses 10 functional clusters (Figure 2A). The DNA repair cluster included proteins such as members of the mismatch repair system (MMR: MHS2, MSH6, MLH1) and the double-strand break repair protein MRE11A. These proteins were confirmed to be enriched at nascent DNA in ESCs by western blot with specific antibodies (Figure 3A). The enrichment on MMR proteins at nascent DNA concurs with previous studies in yeast (26) and the more recent iPOND mass-spectrometry data on HEK-293T cells (10,11). These results suggest that DNA repair systems could be an integral part of the replication machinery across different cell types, although analysis of the mutation frequency (12) and total proteins levels between fibroblasts and ESCs (Supplementary Figure S5) indicate quantitative differences in MMR system activity in ESCs and somatic cells.
Affiliation: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden firstname.lastname@example.org.