Yet, mitotic chromatin accessibility does Enhancers, in contrast, show more variable degrees of chromatin accessibility. This is particularly true at active promoters, perhaps reflecting their low but nevertheless significant mitotic activity,Īs recently reported ( Palozola et al. Is highly condensed during mitosis, gene regulatory elements remain globally accessible ( Hsiung et al. These features would represent the inherited properties drivingĪnd accelerating the reassembly of functional regulatory complexes early in the following interphase. May preserve specific chromatin features at bookmarked sites. Instead, their transient binding activity Of BFs is not simply mediated by their stable retention at enhancers and promoters. BFs are highly dynamic during mitosis and often exhibit reduced residence times on the chromatin. Nonetheless, the molecular mechanisms underpinning this function remain to be elucidated ( Festuccia et al. Information from mother to daughter cells, as illustrated by GATA1 ( Kadauke et al. These TFs, known as mitotic bookmarking factors (BFs), are believed to directly convey gene regulatory One potential mechanism is known as mitotic bookmarking: Some TFs have the ability to interact with their DNA binding sitesĭuring cell division. The mechanisms by which daughter cells accurately re-establish an environment permissive for efficient transcriptional activationĮarly in interphase remain unknown ( de Castro et al. Therefore, many processes occur simultaneously to temporarily halt gene regulation and transcription during mitosis. This process naturally inhibits the ability of TFs to scan DNA for their binding ![]() Moreover, the breakdown of the nuclear envelope, and the consequent increase of the volume that TFs can freely explore, 2011) but has also been observed for other TFs such as POU5F1 (also known as OCT4) and SOX2 ( Qi et al. Phosphorylation of C2H2 zinc finger TFs such as YY1 ( Rizkallah and Hurt 2009 Rizkallah et al. This is particularly well illustrated by the systematic Mitosis, leading to an intrinsic reduction of their ability to bind DNA. Loss of TF binding is further accentuated by the stereotypical phosphorylation of many regulators during This leads to a strong decrease in transcriptional activity and to the general reduction of transcription factor (TF) binding Provide a mechanistic framework that reconciles dynamic mitotic binding with the transmission of gene regulatory informationĭuring mitosis, the chromatin is drastically condensed and reconfigured to enable the equitable partition of the genetic materialīetween the two daughter cells ( Ma et al. The rapid post-mitotic re-establishment of functional regulatory complexes at selected enhancers and promoters. By maintaining nucleosome positioning during mitosis, ESRRB might ensure That ordered nucleosomal arrays are retained during mitosis at ESRRB bookmarked sites, whereas regions losing transcriptionįactor binding display a profound loss of order. ![]() ![]() Mitotic chromosomes, either throughout the chromosomal arms (SOX2) or at pericentromeric regions (POU5F1). Regulatory regions in mitosis, SOX2 and POU5F1 (also known as OCT4) establish DNA sequence-independent interactions with the Of previously proposed BFs in embryonic stem cells: While ESRRB can be considered as a canonical BF that binds at selected Here, comparing formaldehyde to alternative fixatives we clarify the nature of the chromosomal association Second, if BFs are not permanently bound to their targets during mitosis, it becomes unclear how they convey regulatory information To be unable to efficiently capture these transient interactions, leading to profound contradictions in the literature and This represents bothĪ technical and a conceptual challenge to study and understand the function of BFs: First, formaldehyde has been suggested Occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. While they were thought to propagate gene regulatory information through mitosis by statically Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major
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