Coexpression of Brn‐3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis

Hudson, Chris; Podesta, Jennifer E.; Henderson, Deborah J.; Latchman, DS; Budhram-Mahadeo,

doi:10.1002/jnr.20299

Cited by 17 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We first investigated whether Brn-3a and p73 are co-expressed in a developmentally relevant model by undertaking co-immunostaining studies in primary cultures of neural crest cells (NCC) that give rise to sensory neurons, and are known to express Brn-3a. 26,27 As expected, Brn-3a was expressed in two populations of NCC-derived cells. Figure 1a shows that the larger flattened differentiated cells with neurite outgrowth express both p73 and Brn-3a whereas Figure 1b shows that the smaller, rounded undifferentiated Brn-3a expressing NCC 26 are negative for p73.…”

supporting

confidence: 64%

“…26,27 As expected, Brn-3a was expressed in two populations of NCC-derived cells. Figure 1a shows that the larger flattened differentiated cells with neurite outgrowth express both p73 and Brn-3a whereas Figure 1b shows that the smaller, rounded undifferentiated Brn-3a expressing NCC 26 are negative for p73. Figure 1c and Supplementary Figure S1A show that when co-localized in NCC, both p73 and Brn-3a show nuclear expression.…”

supporting

confidence: 64%

“…First, p73 proteins co-localized with Brn-3a in differentiated sensory neurons (but not in undifferentiated Brn-3a-positive cells) arising from a developmentally relevant model of pluripotent progenitor NCC cultures. 26 Brn-3a is essential for the survival and differentiation of sensory neurons in the developing peripheral nervous system 3,27,34 so that its co-expression with p73 proteins is likely to be of relevance for fate determination. Brn-3aÀ/À mutants suffer significant loss of sensory neurons by apoptosis during development, and this correlated with elevated Bax expression.…”

Section: Actinmentioning

confidence: 99%

See 2 more Smart Citations

Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription

et al. 2008

View full text Add to dashboard Cite

The Brn-3a/POU4F1 POU transcription factor is critical for the survival and differentiation of specific sensory neurons during development or upon injury; by regulating expression of target genes, either directly or indirectly upon interaction with other proteins. In this study, we demonstrated the physical interaction of Brn-3a with different p73 isoforms and showed co-localization in sensory neurons arising from the neural crest. The biological effects of p73/ Brn-3a interaction depend on the particular p73 isoform, because co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and DNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but cooperated to increase transcription of the cell cycle regulator p21 CIP1/Waf1 . The region 425-494 amino acids within the TAp73 C terminus were critical for Brn-3a to repress Bax transactivation, but not for cooperation on the p21 CIP1/Waf1 promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21 CIP1/Waf1 promoter and that Brn-3a modulates this interaction. Thus, the physical interaction of Brn-3a with specific p73 isoforms will be critical for determining cell fate during neuronal development or in injured neurons expressing both factors. Cell Death and Differentiation (2008) The Brn-3a POU transcription factor (also referred to as POU4F1) is expressed in sensory neurons of the central nervous system and peripheral nervous system, for review see Phillips K and Luisi B; Latchman DS. 1,2 It is essential for the survival and normal differentiation of these neurons during development since loss of Brn-3a in knockout (KO) mice results in extensive apoptosis of somato-sensory neurons with subsequent death of mutants mice by postnatal day 1 (P1). 3,4 Brn-3a enhances the survival of neuronal cultures prepared from dorsal root ganglia and trigeminal ganglia following neurotrophic withdrawal, whereas loss of Brn-3a results in apoptosis even in the presence of neurotrophic factors. 5,6 Increasing Brn-3a also enhances neuronal survival following nerve injury, for example in sciatic nerve crush. 7 Brn3a is also important for neuronal differentiation since Brn-3a KO mice have defects in neurite outgrowth. 8 Brn-3a/bax double KO mutants were used to further dissect these events since sensory neurons in these double KO survived during development but failed to express the Brn-3a target gene, TrkA, and showed abnormal differentiation. 9 Brn-3a exists as two isoforms that are identical in the C terminus containing the POU domain, but the longer 46 kDa Brn-3a(l) contains an amino N-terminal transactivation domain (TAD) that is absent in the shorter 35 kDa Brn-3a(s) protein, 10 (see Figure 2a). Brn-3a(l) is essential for neuronal survival because mutant mice lacking the N-terminal TAD alone demonstrate neuronal loss and lethality, similar to full Brn-3a KO mice. 11The p53 family proteins, namely p53, p63 and p73, are structurally rela...

show abstract

supporting

confidence: 64%

supporting

confidence: 64%

Section: Actinmentioning

confidence: 99%

See 1 more Smart Citation

Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Moreover, Wnt7b was found to be one of the new putative p53 target genes during NGF-mediated PC12 neuronal differentiation [86]. Studies in neuronal cells have suggested that the interaction of p53 with the neuron-specific and pro-differentiation TF BRN3A facilitates a shift of p53 transcriptional activity from cell death to neuronal differentiation [87]. As there are approximately 12 000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP/p300 in a neuronal activity-dependent manner, the function of CBP/p300 at enhancers may be to recruit RNAPII together with p53, as activity-regulated RNAPII binding to thousands of enhancers has been observed [50].…”

Section: Cell-intrinsic Epigenetic Mechanisms Targeted By Cell-cycle mentioning

confidence: 99%

Epigenetic setting and reprogramming for neural cell fate determination and differentiation

Imamura

Uesaka

Nakashima

2014

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

In the mammalian brain, epigenetic mechanisms are clearly involved in the regulation of self-renewal of neural stem cells and the derivation of their descendants, i.e. neurons, astrocytes and oligodendrocytes, according to the developmental timing and the microenvironment, the 'niche'. Interestingly, local epigenetic changes occur, concomitantly with genome-wide level changes, at a set of gene promoter regions for either down-or upregulation of the gene. In addition, intergenic regions also sensitize the availability of epigenetic modifiers, which affects gene expression through a relatively long-range chromatinic interaction with the transcription regulatory machineries including non-coding RNA (ncRNA) such as promoter-associated ncRNA and enhancer ncRNA. We show that such an epigenetic landscape in a neural cell is statically but flexibly formed together with a variable combination of generally and locally acting nuclear molecules including master transcription factors and cell-cycle regulators. We also discuss the possibility that revealing the epigenetic regulation by the local DNA -RNA -protein assemblies would promote methodological innovations, e.g. neural cell reprogramming, engineering and transplantation, to manipulate neuronal and glial cell fates for the purpose of medical use of these cells.

show abstract

“…62 However, a switch in POU TFs from BRN1/2 to BRN3a occurs in post-mitotic cells. 63 HMGA2. High mobility group A2 (HMGA2) is a chromatin associated protein that potentiates the activity of TFs.…”

Section: Gli-2 Gli-3 (Zfp)mentioning

confidence: 99%

Transcription factors and neural stem cell self-renewal, growth and differentiation

Ahmed

Gan

Lam

et al. 2009

Cell Adhesion & Migration

View full text Add to dashboard Cite

The central nervous system (CNS) is a large network of interconnecting and intercommunicating cells that form functional circuits. Disease and injury of the CNS are prominent features of the healthcare landscape. There is an urgent unmet need to generate therapeutic solutions for CNS disease/injury. To increase our understanding of the CNS we need to generate cellular models that are experimentally tractable. Neural stem cells (NSCs), cells that generate the CNS during embryonic development, have been identified and propagated in vitro. To develop NSCs as a cellular model for the CNS we need to understand more about their genetics and cell biology. In particular, we need to define the mechanisms of self-renewal, proliferation and differentiation-i.e. NSC behavior. The analysis of pluripotency of embryonic stem cells through mapping regulatory networks of transcription factors has proven to be a powerful approach to understanding embryonic development. Here, we discuss the role of transcription factors in NSC behavior.

show abstract

Coexpression of Brn‐3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis

Cited by 17 publications

References 47 publications

Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription

Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription

Epigenetic setting and reprogramming for neural cell fate determination and differentiation

Transcription factors and neural stem cell self-renewal, growth and differentiation

Contact Info

Product

Resources

About