Mitotic partitioning of transcription factors

Abstract

Mitosis is a highly orchestrated process involving numerous protein kinases and phosphatases. At the onset of mitosis, the chromatin condensation into metaphase chromosomes is correlated with global phosphorylation of histone H3. The bulk of transcription is silenced while many of the transcription-associated proteins, including transcription and chromatin remodeling factors, are excluded from chromatin, typically as a consequence of their phosphorylation. Components of the transcription machinery and regulatory proteins are recycled and equally partitioned between newly divided cells by mechanisms that may involve microtubules, microfilaments or intermediate filaments.However, as demonstrated in the case of Runx2, a subset of transcription factors involved in lineage-specific control, likely remain associated with their target genes to direct the deposition or removal of epigenetic marks. The displacement and re-entry into daughter cells of transcription and chromatin remodeling factors are temporally defined and regulated. Reformation of daughter nuclei is a critical time to reestablish the proper gene expression pattern. The mechanisms involved in the marking and re-establishment of gene expression has been elucidated for few genes. The elucidation of how the memory of a programmed expression profile is transmitted to daughter cells represents a challenge. J. Cell. Biochem. 105: 1-8, 2008. ß 2008 Wiley-Liss, Inc. KEY WORDS: MITOSIS; GENE EXPRESSION; EPIGENETIC MARKS; TRANSCRIPTION FACTORS; CHROMATIN REMODELING; PHOSPHORYLATIONA t the onset of mitosis, while chromosome condensation takes place to facilitate segregation of sister chromatids between daughter cells, the nuclear envelope ruptures and the bulk of transcription activity ceases. The entry into mitosis is also characterized by extensive protein phosphorylation. The condensation of interphase chromatin into mitotic chromosomes, restricting the accessibility of DNA to transcription factors and RNA polymerases, has been put forward as the most evident mechanism of transcription shut-down [Gottesfeld and Forbes, 1997]. However, on and off exchanges of transcription factors and nucleosome components were observed from condensed mitotic chromosomes, suggesting that transcription arrest is due to reasons other than chromatin condensation itself [Chen et al., 2005]. Alternative mechanisms include inactivation by phosphorylation and/or displacement of RNA polymerases, chromatin remodeling complexes and transcription factors from mitotic chromosomes [Gottesfeld and Forbes, 1997;John and Workman, 1998]. When cells exit mitosis, specific gene expression patterns must be reestablished. It has been proposed that a subset of factors act as molecular bookmarks by binding to mitotic chromatin, as genes poised for reactivation are marked by protein-dependent structural distortions [Michelotti et al., 1997]. Several studies providing evidence to support this hypothesis are reviewed here. Furthermore, the elucidation of the spatial and temporal mitotic reorganiza...

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

“…Because transcription-related factors are excluded from mitotic chromatin, mitotic chromosomes are transcriptionally inactive [15]. In contrast, some markers for epigenetic gene control are retained during mitosis [22]. It is possible that transcription and the formation of higher order chromatin structures mediated by CTCF might result in a disadvantage to achieve accurate chromosome segregation; however, we found that a part of CTCF still interacts with mitotic chromatin as reported previously ( Fig.…”

Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit

“…This time frame is less consistent with rapid signal transduction events and more consistent with gradual accumulation of prodeath signals (10,35). Given that most transcription factors are displaced from mitotic chromatin, it has been postulated that the decay of mRNAs may influence cell fates during prolonged mitotic block (35,36). We predict that the differential decay of mRNAs encoding proteins that influence apoptotic cell death during mitosis leads to a gradual inclination toward death.…”

Active transcription and essential role of RNA polymerase II at the centromere during mitosis

“…It also indicates that RNAPII binding at the kinetochore is DNA sequence independent and does not require large tracts of repeat DNA. With few exceptions, mitosis has long been assumed to be a period of transcriptional silence, characterized by the eviction of both RNAPII and transcription factors from the bulk mitotic chromatin (25)(26)(27). In view of the dogma of mitotic gene repression, our demonstration of specific retention of RNAPII, CTDP1, and SSRP1 at the mitotic kinetochore and evidence of centromeric mitotic transcription is striking.…”