Abstract
The chromatin-associated proteome (chromatome) regulates cellular gene expression by restricting access of transcriptional machinery to template DNA, and dynamic re-modeling of chromatin structure is required to regulate critical cell functions including growth and replication, DNA repair and recombination, and oncogenic transformation in progression to cancer. Central to the control of these processes is efficient regulation of the host cell cycle, which is maintained by rapid changes in chromatin conformation during normal cycle progression. A global overview of chromatin protein organization is therefore essential to fully understand cell cycle regulation, but the influence of the chromatome and chromatin binding topology on host cell cycle progression remains poorly defined. Here we used partial MNase digestion together with iTRAQ-based high-throughput quantitative proteomics to quantify chromatin-associated proteins during interphase progression. We identified a total of 481 proteins with high confidence that were involved in chromatin-dependent events including transcriptional regulation, chromatin re-organization, and DNA replication and repair, whereas the quantitative data revealed the temporal interactions of these proteins with chromatin during interphase progression. When combined with biochemical and functional assays, these data revealed a strikingly dynamic association of protein HP1BP3 with the chromatin complex during different stages of interphase, and uncovered a novel regulatory role for this molecule in transcriptional regulation. We report that HP1BP3 protein maintains heterochromatin integrity during G1-S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity.
Highlights
The eukaryotic cell cycle consists of two major consecutive events: duplication of the genome by DNA synthesis and distribution of the duplicated genome into daughter cells via mitosis
We further report that novel chromatin protein HP1BP3 maintains heterochromatin integrity during G1–S progression in order to regulate the duration of G1 phase and thereby control cell proliferation
The current study provides the first detailed profile of the chromatin-associated proteome during cell cycle progression and identifies chromatome protein HP1BP3 as a novel regulator of cell proliferation
Summary
The eukaryotic cell cycle consists of two major consecutive events: duplication of the genome by DNA synthesis and distribution of the duplicated genome into daughter cells via mitosis. Rapid access to the DNA template during interphase is achieved by maintaining chromatin in a highly dynamic state [1, 2], and is required for the efficient transmission of genetic and epigenetic information into daughter cells via careful regulation of the host cell cycle [3, 4]. Transmission of epigenetic information from mother cell to daughter cells (epigenetic inheritance) is mediated via DNA and histone modifications, histone variants, non-histone chromatin proteins, nuclear RNA, and changes in higher-order chromatin structure (9 –13). Recent data indicate that non-histone proteins including RNA polymerase III, topoisomerase II ␣, heterochromatin protein 1, and high-mobility group nucleosome-binding proteins (HMGNs) critically influence chromatin structural dynamics (29 –33), but current data are insufficient to fully establish the role played by chromatin-associated proteins in the control of the host cell cycle. Our approach of constructing a global picture of chromatin-associated protein dynamics during interphase progression may allow future studies to better determine the influence of chromatin biology on other cellular processes and disease pathogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
