scholarly journals H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development

2018 ◽  
Vol 47 (2) ◽  
pp. 607-620 ◽  
Author(s):  
Younghoon Jang ◽  
Aaron Broun ◽  
Chaochen Wang ◽  
Young-Kwon Park ◽  
Lenan Zhuang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tissue Development ◽  
Adipose Tissue Development ◽  
H3k4 Methyltransferases

scholarly journals H3.3K4M destabilizes enhancer epigenomic writers MLL3/4 and impairs adipose tissue development

2018 ◽  
Author(s):  
Younghoon Jang ◽  
Chaochen Wang ◽  
Aaron Broun ◽  
Young-Kwon Park ◽  
Lenan Zhuang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Precursor Cells ◽  
Tissue Development ◽  
Set Domain ◽  
H3k4 Methylation ◽  
Double Knockout ◽  
Histone H3k4 ◽  
Adipose Tissue Development ◽  
And Function ◽  
H3k4 Methyltransferases

AbstractHistone H3K4 mono-methyltransferases MLL3 and MLL4 (MLL3/4) are required for enhancer activation during cell differentiation, though the mechanism is incompletely understood. To address MLL3/4 enzymatic activity in enhancer regulation, we have generated two mouse lines: one expressing H3.3K4M, a lysine-4-to-methionine (K4M) mutation of histone H3.3 that inhibits H3K4 methylation, and the other carrying conditional double knockout of MLL3/4 enzymatic SET domains. Expression of H3.3K4M in lineage-specific precursor cells depletes H3K4 methylation and prevents adipogenesis and adipose tissue development. Mechanistically, H3.3K4M prevents enhancer activation in adipogenesis by destabilizing MLL3/4 proteins but not other Set1-like H3K4 methyltransferases. Notably, deletion of the enzymatic SET domain of MLL3/4 in lineage-specific precursor cells mimics H3.3K4M expression and prevents adipose tissue development. Interestingly, destabilization of MLL3/4 by H3.3K4M in adipocytes does not affect adipose tissue maintenance and function. Together, our findings indicate that H3.3K4M destabilizes enhancer epigenomic writers MLL3/4 and impairs adipose tissue development.

ADAMTS13 deficiency in mice does not affect adipose tissue development

2015 ◽  
Vol 1850 (7) ◽  
pp. 1368-1374 ◽  
Author(s):  
Lotte Geys ◽  
Ilse Scroyen ◽  
Elien Roose ◽  
Karen Vanhoorelbeke ◽  
Henri Roger Lijnen
Keyword(s):  
Adipose Tissue ◽  
Tissue Development ◽  
Adipose Tissue Development ◽  
Adamts13 Deficiency
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