Abstract:During development, transcriptional properties of progenitor cells are stably propagated across multiple cellular divisions. Yet, at each division, chromatin faces structural constraints imposed by the important nuclear re-organization operating during mitosis. It is now clear that not all transcriptional regulators are ejected during mitosis, but rather that a subset of transcription factors, chromatin regulators and epigenetic histone marks are able to ‘bookmark’ specific loci, thereby providing a mitotic me… Show more
“…Given the various well characterized steps required prior to productive transcriptional elongation (e.g. promoter opening, transcription factor binding, pre-initiation complex recruitment…), it is reasonable to consider a series of transitions that a promoter must travel through prior to activation, with an allocated duration 11 , 24 . Fig.…”
Section: Resultsmentioning
confidence: 99%
“…In addition to these properties, classical pioneer factors bind nucleosomes and are typically retained on the chromosomes during mitosis 10 , 11 . Mitotic retention of these transcription factors places them as ideal candidates for the transmission of chromatin states during cellular divisions, through a mitotic bookmarking mechanism.…”
Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence. However, the impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains unclear. Here we employ quantitative live imaging methods and mathematical modeling to test the effect of the pioneer factor Zelda on transcriptional dynamics and memory in Drosophila embryos. We demonstrate that increasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past. Despite its known pioneering activities, we show that Zelda does not remain detectably associated with mitotic chromosomes and is neither necessary nor sufficient to foster memory. We further reveal that Zelda forms sub-nuclear dynamic hubs where Zelda binding events are transient. We propose that Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps.
“…Given the various well characterized steps required prior to productive transcriptional elongation (e.g. promoter opening, transcription factor binding, pre-initiation complex recruitment…), it is reasonable to consider a series of transitions that a promoter must travel through prior to activation, with an allocated duration 11 , 24 . Fig.…”
Section: Resultsmentioning
confidence: 99%
“…In addition to these properties, classical pioneer factors bind nucleosomes and are typically retained on the chromosomes during mitosis 10 , 11 . Mitotic retention of these transcription factors places them as ideal candidates for the transmission of chromatin states during cellular divisions, through a mitotic bookmarking mechanism.…”
Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence. However, the impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains unclear. Here we employ quantitative live imaging methods and mathematical modeling to test the effect of the pioneer factor Zelda on transcriptional dynamics and memory in Drosophila embryos. We demonstrate that increasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past. Despite its known pioneering activities, we show that Zelda does not remain detectably associated with mitotic chromosomes and is neither necessary nor sufficient to foster memory. We further reveal that Zelda forms sub-nuclear dynamic hubs where Zelda binding events are transient. We propose that Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps.
“…During mitosis, transcription factors (TFs) and other chromatin‐binding factors dissociate from condensing chromatin, with loss of the high order chromatin organization thought to define cell state, such as active and inactive chromatin compartments (known as “A” and “B”) (Fortin & Hansen, 2015; Lieberman‐Aiden et al, 2009), chromatin loops and topologically associating domains (TADs). Some factors remain bound to chromatin throughout mitosis, however, a phenomenon known as mitotic bookmarking (Bellec, Radulescu, & Lagha, 2018; Festuccia, Gonzalez, Owens, & Navarro, 2017; Kadauke & Blobel, 2013; Teves et al, 2016), which is thought to allow cells in early G1 to re‐establish their unique chromatin conformation (Nagano et al, 2017; H. Zhang et al, 2019). The condensation and re‐expansion of chromatin during mitosis and the transition to G1 may represent an opportunity for cell fate reprogramming.…”
Essentially all cell cycling in multicellular organisms in vivo takes place in the context of lineage differentiation. This notwithstanding, the regulation of the cell cycle is often assumed to be generic, independent of tissue or developmental stage. Here we review developmental‐stage‐specific cell cycle adaptations that may influence developmental decisions, in mammalian erythropoiesis and in other lineages. The length of the cell cycle influences the balance between self‐renewal and differentiation in multiple tissues, and may determine lineage fate. Shorter cycles contribute to the efficiency of reprogramming somatic cells into induced pluripotency stem cells and help maintain the pluripotent state. While the plasticity of G1 length is well established, the speed of S phase is emerging as a novel regulated parameter that may influence cell fate transitions in the erythroid lineage, in neural tissue and in embryonic stem cells. A slow S phase may stabilize the self‐renewal state, whereas S phase shortening may favor a cell fate change. In the erythroid lineage, functional approaches and single‐cell RNA‐sequencing show that a key transcriptional switch, at the transition from self‐renewal to differentiation, is synchronized with and dependent on S phase. This specific S phase is shorter, as a result of a genome‐wide increase in the speed of replication forks. Furthermore, there is progressive shortening in G1 in the period preceding this switch. Together these studies suggest an integrated regulatory landscape of the cycle and differentiation programs, where cell cycle adaptations are controlled by, and in turn feed back on, the propagation of developmental trajectories.
This article is categorized under:
Congenital Diseases > Stem Cells and Development
“…Le suivi de l'activation de la transcription dans des embryons vivants est possible grâce à l'ajout, dans une partie non-codante du transgène rapporteur, de séquences de fixation de la protéine du bactériophage MS2 à l'ARN [6]. Lors de la transcrip-Zelda, le maestro du réveil du génome zygotique de « marque-pages » [8]. Les facteurs de transcription « pionniers », outre leur propriété de se lier aux nucléosomes, restent généralement associés aux chromosomes mitotiques.…”
Section: Zelda Favorise La Coordination Temporelle De La Transcriptionunclassified
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