Topic
NpBAF complex
About: NpBAF complex is a research topic. Over the lifetime, 2 publications have been published within this topic receiving 525 citations.
Papers
TL;DR: It is found that BAF53a repression is mediated by sequences in the 3′ untranslated region corresponding to the recognition sites for miR-9* and miR -124, which are selectively expressed in post-mitotic neurons.
Abstract: A key step in the development of the vertebrate nervous system occurs when cells exit the multipotent neural stem cell state and enter a phase of post-mitotic neural development. This involves a switch in subunit composition of the SWI/SNF-like BAF chromatin remodelling complexes. Here, Yoo et al. show that the switch in BAF subunits is mediated by two microRNAs that are selectively expressed in post-mitotic neurons. During development of the vertebrate nervous system, a switch in the subunit composition of the BAF chromatin-remodelling complex occurs when cells lose multipotency and begin to develop stable connections that will persist for a lifetime. Here, the switch in BAF subunits is shown to be mediated by two microRNAs that are selectively expressed in post-mitotic neurons. One of the most distinctive steps in the development of the vertebrate nervous system occurs at mitotic exit when cells lose multipotency and begin to develop stable connections that will persist for a lifetime1,2. This transition is accompanied by a switch in ATP-dependent chromatin-remodelling mechanisms that appears to coincide with the final mitotic division of neurons. This switch involves the exchange of the BAF53a (also known as ACTL6a) and BAF45a (PHF10) subunits within Swi/Snf-like neural-progenitor-specific BAF (npBAF) complexes for the homologous BAF53b (ACTL6b) and BAF45b (DPF1) subunits within neuron-specific BAF (nBAF) complexes in post-mitotic neurons. The subunits of the npBAF complex are essential for neural-progenitor proliferation, and mice with reduced dosage for the genes encoding its subunits have defects in neural-tube closure similar to those in human spina bifida3, one of the most serious congenital birth defects. In contrast, BAF53b and the nBAF complex are essential for an evolutionarily conserved program of post-mitotic neural development and dendritic morphogenesis4,5. Here we show that this essential transition is mediated by repression of BAF53a by miR-9* and miR-124. We find that BAF53a repression is mediated by sequences in the 3′ untranslated region corresponding to the recognition sites for miR-9* and miR-124, which are selectively expressed in post-mitotic neurons. Mutation of these sites led to persistent expression of BAF53a and defective activity-dependent dendritic outgrowth in neurons. In addition, overexpression of miR-9* and miR-124 in neural progenitors caused reduced proliferation. Previous studies have indicated that miR-9* and miR-124 are repressed by the repressor-element-1-silencing transcription factor (REST, also known as NRSF)6. Indeed, expression of REST in post-mitotic neurons led to derepression of BAF53a, indicating that REST-mediated repression of microRNAs directs the essential switch of chromatin regulatory complexes.
625 citations
TL;DR: It is proposed that the function of the npBAF to nBAF chromatin switch is to control progenitor cell cycle exit and promote synchronous neural differentiation.
Abstract: Nervous system development is orchestrated by tightly-regulated progenitor cell divisions, followed by differentiation at precise but varying times across different regions. As progenitors exit the cell cycle, they initiate a subunit switch of the mSWI/SNF or npBAF complex to generate neuron-specific nBAF complexes. These chromatin regulatory complexes play dosage-sensitive roles in neural development and are frequently mutated in neurodevelopmental disorders. Here we manipulated the timing of BAF subunit exchange in the developing mouse brain and find that deletion of the npBAF subunit BAF53a blocks progenitor proliferation, leading to impaired neurogenesis. We show that npBAF complexes regulate cell cycle progression by antagonizing Polycomb complexes to promote chromatin accessibility at cell cycle and NPC identity genes. Replacement of the actin-related protein, Actl6a (BAF53a) by the neuron-specific actin-related protein, Actl6b (BAF53b), but not other regulators of proliferation, rescues progenitors by promoting neuronal differentiation. We propose that the function of the npBAF to nBAF chromatin switch is to control progenitor cell cycle exit and promote synchronous neural differentiation.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 1 |
| 2009 | 1 |