Abstract
Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin remodeling complexes. Carefully controlled, global Brg1 protein depletion in X. tropicalis and X. laevis causes embryonic lethality or developmental arrest from gastrulation on. Transcriptome analysis at late blastula, before development becomes arrested, indicates predominantly a role for Brg1 in transcriptional activation of a limited set of genes involved in pattern specification processes and nervous system development. Mosaic analysis by targeted microinjection defines Brg1 as an essential amplifier of gene expression in dorsal (BCNE/Nieuwkoop Center) and ventral (BMP/Vent) signaling centers. Moreover, Brg1 is required and sufficient for initiating axial patterning in cooperation with maternal Wnt signaling. In search for a common denominator of Brg1 impact on development, we have quantitatively filtered global mRNA fluctuations at MBT. The results indicate that Brg1 is predominantly required for genes with the highest burst of transcriptional activity. Since this group contains many key developmental regulators, we propose Brg1 to be responsible for raising their expression above threshold levels in preparation for embryonic patterning.
Highlights
Vertebrate BAF protein complexes remodel chromatin with the mutually exclusive help of Brahma or Brahma-related gene 1 ATPase subunits
We investigated the consequences of systemic Brahma related gene 1 (Brg1) protein knockdown in X. tropicalis embryos, where the target region for BMO1 and BMO2 is conserved (Fig 1A)
The survival rate of CoMO and BMO1 morphants was comparable until late blastula, the Brg1 protein levels were already diminished in the latter case to about 30% of CoMO injected embryos (Fig 1C)
Summary
Vertebrate BAF protein complexes remodel chromatin with the mutually exclusive help of Brahma (brm) or Brahma-related gene 1 (brg1) ATPase subunits. SWI/SNF complexes are known to participate broadly in nucleosome-based aspects of DNA metabolism in normal and malignant cells [1,2,3,4], but their specific ATPase subunits designate them for different functions. Brg1-/- mice die during early embryogenesis and brg heterozygotes are predisposed to exencephaly and tumor formation [6]. These results suggest unique functions for BAF complexes carrying the different ATPases. Specific functions have been described in murine embryonic stem cells, where a specialized esBAF complex containing Brg, Baf155 and Baf60a regulates aspects of ES self renewal, pluripotency and cell priming for differentiation [9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
