The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F20%3A00539949" target="_blank" >RIV/68378041:_____/20:00539949 - isvavai.cz</a>
Result on the web
<a href="https://www.jbc.org/article/S0021-9258(17)48561-9/fulltext" target="_blank" >https://www.jbc.org/article/S0021-9258(17)48561-9/fulltext</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1074/jbc.RA120.012684" target="_blank" >10.1074/jbc.RA120.012684</a>
Alternative languages
Result language
angličtina
Original language name
The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice
Original language description
Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1(Cre)-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1(Cre),Meis2(f/f) mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10605 - Developmental biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Biological Chemistry
ISSN
0021-9258
e-ISSN
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Volume of the periodical
295
Issue of the periodical within the volume
16
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
5449-5460
UT code for WoS article
000530288000021
EID of the result in the Scopus database
2-s2.0-85083575339