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PLoS Genet 2017 May 12;135:e1006757. doi: 10.1371/journal.pgen.1006757.
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Brg1 chromatin remodeling ATPase balances germ layer patterning by amplifying the transcriptional burst at midblastula transition.

Wagner G , Singhal N , Nicetto D , Straub T , Kremmer E , Rupp RAW .

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.

PubMed ID: 28498870
PMC ID: PMC5428918
Article link: PLoS Genet

Species referenced: Xenopus
Genes referenced: actc1 bmp4 casp3.2 cer1 chrd ctnnb1 egr1 f10 fadd foxa4 foxd4l1.1 foxd4l1.2 fst gata4 gs17 gsc hhex myf5 myod1 nodal nodal3.1 nog otx2 post sia1 smarca4 sox21 tbxt ventx1 ventx1.2 ventx2 ventx2.2 zic1 zic2
Morpholinos: smarca4 MO2 smarca4 MO3 smarca4 MO4

GEO Series: GSE82017: NCBI
GSE82018: NCBI
GSE82019: NCBI

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References [+] :
Aldiri, Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma. 2015, Pubmed