Document Detail


Multiple epigenetic maintenance factors implicated by the loss of Mll2 in mouse development.
MedLine Citation:
PMID:  16540515     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epigenesis is the process whereby the daughters of a dividing cell retain a chromatin state determined before cell division. The best-studied cases involve the inheritance of heterochromatic chromosomal domains, and little is known about specific gene regulation by epigenetic mechanisms. Recent evidence shows that epigenesis pivots on methylation of nucleosomes at histone 3 lysines 4, 9 or 27. Bioinformatics indicates that mammals have several enzymes for each of these methylations, including at least six histone 3 lysine 4 methyltransferases. To look for evidence of gene-specific epigenetic regulation in mammalian development, we examined one of these six, Mll2, using a multipurpose allele in the mouse to ascertain the loss-of-function phenotype. Loss of Mll2 slowed growth, increased apoptosis and retarded development, leading to embryonic failure before E11.5. Using chimera experiments, we demonstrated that Mll2 is cell-autonomously required. Evidence for gene-specific regulation was also observed. Although Mox1 and Hoxb1 expression patterns were correctly established, they were not maintained in the absence of Mll2, whereas Wnt1 and Otx2 were. The Mll2 loss-of-function phenotype is different from that of its sister gene Mll, and they regulate different Hox complex genes during ES cell differentiation. Therefore, these two closely related epigenetic factors play different roles in development and maintain distinct gene expression patterns. This suggests that other epigenetic factors also regulate particular patterns and that development entails networks of epigenetic specificities.
Authors:
Stefan Glaser; Julia Schaft; Sandra Lubitz; Kristina Vintersten; Frank van der Hoeven; Katharina R Tufteland; Rein Aasland; Konstantinos Anastassiadis; Siew-Lan Ang; A Francis Stewart
Related Documents :
17556365 - Characterizing early events associated with the activation of target genes by 1,25-dihy...
18269915 - Ngf/pi3k signaling-mediated epigenetic regulation of delta opioid receptor gene express...
17637845 - Intergenic transcription, cell-cycle and the developmentally regulated epigenetic profi...
19897725 - A histone demethylase is necessary for regeneration in zebrafish.
9506835 - Characterization of the internal promoter of human t-cell leukemia virus type i.
22045915 - Tissue- and cell-type specific transcriptome profiling of expanding tomato fruit provid...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-15
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  133     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-24     Completed Date:  2006-06-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  1423-32     Citation Subset:  IM    
Affiliation:
Genomics, BioInnovationsZentrum, Dresden University of Technology, Am Tatzberg 47, Dresden 01307, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alleles
Animals
Apoptosis / genetics
Cell Line
Epigenesis, Genetic / physiology*
Female
Fetal Growth Retardation / genetics
Gene Deletion*
Gene Expression Regulation, Developmental / physiology
Genes, Lethal
Mice
Mice, Knockout
Mice, Transgenic
Myeloid-Lymphoid Leukemia Protein / deficiency*,  genetics*,  physiology
Phenotype
Chemical
Reg. No./Substance:
0/Mll2 protein, mouse; 149025-06-9/Myeloid-Lymphoid Leukemia Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  FGF9 promotes survival of germ cells in the fetal testis.
Next Document:  Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenes...