Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells

Hau, Ann-Christin; Mommaerts, E. B.; Laub, Vera; Müller, Tanja; Dittmar, Gunnar; Schulte, Dorothea

doi:10.1038/s41598-021-99968-5

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…This scaffolding is directed by weak compartment-driven interactions, loop-extrusion and especially by site-and cell-state-specific looping interactions. Since the anchors of distinct loops are marked by H3K4me1 and H3K27Ac (promoter and element A) already in the ESC state, we speculate that these interactions are driven by NPC-specific TFs, perhaps including PAX6, a master regulator of NPC development, and its cofactors, rather than by H3K27Ac itself [42][43][44][45] . Other TFs have been previously demonstrated to participate in cell type specific looping and PAX6 has been found binding at the base of the NPC-specific loops 40,46,47 .…”

Section: Discussionmentioning

confidence: 96%

A Scaffolding Element Rewires Local 3D Chromatin Architecture During Differentiation

Jerković,

Di Stefano,

Reboul

et al. 2024

Preprint

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Upon differentiation chromatin rewires to reflect its new cellular identity and function. While it is widely known that this process involves cooperative changes in transcription, chromatin composition and 3D conformation, it is unclear what exactly drives these changes and how they influence one another. Here we used ESC-to-NPC differentiation to study rewiring at a 3 Mb large neuronal Zfp608 locus. During this process, this large chromatin domain splits in half right at the Zfp608 promoter, local chromatin gets littered with activating marks, compacts in 3D space and Zfp608 abounds in transcription. We investigated the cis and trans elements using capture Hi-C (cHi-C), extensive biophysical modelling, and 3-colour 3D-FISH with technical and analytical breakthroughs and found that transcription abundance modulates the contacts in the region as well as the insulation at the domain split. Furthermore, we found a genetic element we named scaffolding element, with a dual enhancer and architectural function that is essential for chromatin rewiring and loop formation at the NPC stage. The loss of this element disrupts the formation of all local NPC-loops irrespective if they are anchored in this element or not, highlighting the hierarchical relationship between elements that act as loop anchors. Furthermore, we uncovered that the scaffolding function, although driven by multiple mechanisms, can form loops independent of loop-extrusion and that other molecular attractions were necessary to form NPC-specific contacts in the region. Together, these results demonstrate that a hierarchy of genetic elements in cis allows successful rewiring during differentiation and that multiple trans acting elements contribute to make this rewiring efficient.

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Section: Discussionmentioning

confidence: 96%

A Scaffolding Element Rewires Local 3D Chromatin Architecture During Differentiation

Jerković,

Di Stefano,

Reboul

et al. 2024

Preprint

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“…Of note, PBX1 is important for the differentiation of neural progenitor cells towards a mDA fate 24 . In fact, the neuron-specific gene doublecortin (Dcx) and the dopaminergic neuron marker gene tyrosine hydroxylase (Th) are known to be direct PBX1 target genes 72 . Neuroblasts leave the SVZ and migrate into the olfactory bulb, where they eventually differentiate into different types of interneurons that are constantly replaced in existing circuits as part of lifelong remodeling of the mammalian olfactory system.…”

Section: Pbx1 Structure Development and Function In Regenerative Medi...mentioning

confidence: 99%

Research progress of PBX1 in developmental and regenerative medicine

Chen¹,

Zhuyuan²,

Niu³

et al. 2023

Int. J. Med. Sci.

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Pre-B-cell leukemia transcription factor 1 (PBX1) proteins are a subfamily of evolutionarily conserved atypical homeodomain transcription factors belonging to the superfamily of triple amino acid loop extension homeodomain proteins. PBX family members play crucial roles in the regulation of various pathophysiological processes. This article reviews the research progress on PBX1 in terms of structure, developmental function, and regenerative medicine. The potential mechanisms of development and research targets in regenerative medicine are also summarized. It also suggests a possible link between PBX1 in the two domains, which is expected to open up a new field for future exploration of cell homeostasis, as well as the regulation of endogenous danger signals. This would provide a new target for the study of diseases in various systems.

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“…Zic1 and Zic2 were found evolutionary conserved, as also C. elegans represses the dopaminergic commitment by the same mechanism (Tiveron et al, 2017 ). Pax6, a gene involved in fate commitment, has also been shown to induce interneurons and dopaminergic phenotype exclusively in the presence of Meis2 TF during the pre-differentiation stage (Hau et al, 2021 ).…”

Section: Profiling Of Enscs In the Physiological Environmentmentioning

confidence: 99%

Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease

Murtaj

Butti

Martino

et al. 2023

Front. Cell. Neurosci.

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Neural stem cells (NSCs), an invaluable source of neuronal and glial progeny, have been widely interrogated in the last twenty years, mainly to understand their therapeutic potential. Most of the studies were performed with cells derived from pluripotent stem cells of either rodents or humans, and have mainly focused on their potential in regenerative medicine. High-throughput omics technologies, such as transcriptomics, epigenetics, proteomics, and metabolomics, which exploded in the past decade, represent a powerful tool to investigate the molecular mechanisms characterizing the heterogeneity of endogenous NSCs. The transition from bulk studies to single cell approaches brought significant insights by revealing complex system phenotypes, from the molecular to the organism level. Here, we will discuss the current literature that has been greatly enriched in the “omics era”, successfully exploring the nature and function of endogenous NSCs and the process of neurogenesis. Overall, the information obtained from omics studies of endogenous NSCs provides a sharper picture of NSCs function during neurodevelopment in healthy and in perturbed environments.

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Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells

Cited by 5 publications

References 52 publications

A Scaffolding Element Rewires Local 3D Chromatin Architecture During Differentiation

A Scaffolding Element Rewires Local 3D Chromatin Architecture During Differentiation

Research progress of PBX1 in developmental and regenerative medicine

Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease

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