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Ino80 is essential for proximal-distal axis asymmetry in part by regulating Bmp4 expression

Overview of attention for article published in BMC Biology, March 2016
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Ino80 is essential for proximal-distal axis asymmetry in part by regulating Bmp4 expression
Published in
BMC Biology, March 2016
DOI 10.1186/s12915-016-0238-5
Pubmed ID

Zhijun Qiu, Zeinab Elsayed, Veronica Peterkin, Suehyb Alkatib, Dorothy Bennett, Joseph W. Landry


Understanding how embryos specify asymmetric axes is a major focus of biology. While much has been done to discover signaling pathways and transcription factors important for axis specification, comparatively little is known about how epigenetic regulators are involved. Epigenetic regulators operate downstream of signaling pathways and transcription factors to promote nuclear processes, most prominently transcription. To discover novel functions for these complexes in axis establishment during early embryonic development, we characterized phenotypes of a mouse knockout (KO) allele of the chromatin remodeling Ino80 ATPase. Ino80 KO embryos implant, but fail to develop beyond the egg cylinder stage. Ino80 KO embryonic stem cells (ESCs) are viable and maintain alkaline phosphatase activity, which is suggestive of pluripotency, but they fail to fully differentiate as either embryoid bodies or teratomas. Gene expression analysis of Ino80 KO early embryos by in situ hybridization and embryoid bodies by RT-PCR shows elevated Bmp4 expression and reduced expression of distal visceral endoderm (DVE) markers Cer1, Hex, and Lefty1. In culture, Bmp4 maintains stem cell pluripotency and when overexpressed is a known negative regulator of DVE differentiation in the early embryo. Consistent with the early embryo, we observed upregulated Bmp4 expression and down-regulated Cer1, Hex, and Lefty1 expression when Ino80 KO ESCs are differentiated in a monolayer. Molecular studies in these same cells demonstrate that Ino80 bound to the Bmp4 promoter regulates its chromatin structure, which correlates with enhanced SP1 binding. These results in combination suggest that Ino80 directly regulates the chromatin structure of the Bmp4 promoter with consequences to gene expression. In contrast to Ino80 KO differentiated cells, our experiments show that undifferentiated Ino80 KO ESCs are viable, but fail to differentiate in culture and in the early embryo. Ino80 KO ESCs and the early embryo up-regulate Bmp4 expression and down-regulate the expression of DVE markers Cer1, Hex and Lefty1. Based on this data, we propose a model where the Ino80 chromatin remodeling complex represses Bmp4 expression in the early embryo, thus promoting DVE differentiation and successful proximal-distal axis establishment. These results are significant because they show that epigenetic regulators have specific roles in establishing embryonic axes. By further characterizing these complexes, we will deepen our understanding of how the mammalian embryo is patterned by epigenetic regulators.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 25%
Student > Bachelor 3 25%
Student > Ph. D. Student 2 17%
Student > Master 2 17%
Other 1 8%
Other 0 0%
Unknown 1 8%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 67%
Agricultural and Biological Sciences 1 8%
Neuroscience 1 8%
Medicine and Dentistry 1 8%
Unknown 1 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 16 March 2016.
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Outputs of similar age
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Outputs of similar age from BMC Biology
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Altmetric has tracked 7,401,456 research outputs across all sources so far. This one has received more attention than most of these and is in the 57th percentile.
So far Altmetric has tracked 823 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.9. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
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 275,610 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.