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Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways

Overview of attention for article published in Human Molecular Genetics, January 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways
Published in
Human Molecular Genetics, January 2016
DOI 10.1093/hmg/ddw010
Pubmed ID
Authors

Matthew A. Lalli, Jiwon Jang, Joo-Hye C. Park, Yidi Wang, Elmer Guzman, Hongjun Zhou, Morgane Audouard, Daniel Bridges, Kenneth R. Tovar, Sorina M. Papuc, Andreea C. Tutulan-Cunita, Yadong Huang, Magdalena Budisteanu, Aurora Arghir, Kenneth S. Kosik

Abstract

Williams syndrome (WS) is a neurodevelopmental disorder caused by a genomic deletion of ∼28 genes that results in a cognitive and behavioral profile marked by overall intellectual impairment with relative strength in expressive language and hypersocial behavior. Advancements in protocols for neuron differentiation from induced pluripotent stem cells allowed us to elucidate the molecular circuitry underpinning the ontogeny of Williams syndrome. In patient-derived stem cells and neurons, we determined the expression profile of the Williams-Beuren Syndrome Critical Region deleted genes and the genome-wide transcriptional consequences of the hemizygous genomic microdeletion at chromosome 7q11.23. Derived neurons displayed disease-relevant hallmarks and indicated novel aberrant pathways in WS neurons including over-activated Wnt signaling accompanying an incomplete neurogenic commitment. We show that haploinsufficiency of the ATP-dependent chromatin remodeler, BAZ1B, which is deleted in WS, significantly contributes to this differentiation defect. Chromatin-immunoprecipitation (ChIP-seq) revealed BAZ1B target gene functions are enriched for neurogenesis, neuron differentiation, and disease-relevant phenotypes. BAZ1B haploinsufficiency caused widespread gene expression changes in neural progenitor cells, and together with BAZ1B ChIP-seq target genes, explained 42% of the transcriptional dysregulation in WS neurons. BAZ1B contributes to regulating the balance between neural precursor self-renewal and differentiation and the differentiation defect caused by BAZ1B haploinsufficiency can be rescued by mitigating over-active Wnt signaling in neural stem cells. Altogether, these results reveal a pivotal role for BAZ1B in neurodevelopment and implicate its haploinsufficiency as a likely contributor to the neurological phenotypes in WS.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 86 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 1%
Unknown 85 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 19%
Student > Master 15 17%
Researcher 12 14%
Student > Bachelor 11 13%
Other 6 7%
Other 10 12%
Unknown 16 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 31 36%
Agricultural and Biological Sciences 13 15%
Neuroscience 6 7%
Medicine and Dentistry 5 6%
Psychology 4 5%
Other 9 10%
Unknown 18 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2016.
All research outputs
#3,237,908
of 22,837,982 outputs
Outputs from Human Molecular Genetics
#1,291
of 8,028 outputs
Outputs of similar age
#58,774
of 394,163 outputs
Outputs of similar age from Human Molecular Genetics
#68
of 115 outputs
Altmetric has tracked 22,837,982 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,028 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.9. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 394,163 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 115 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.