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PMID: 9724755 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 18 ·1998-09-01 ·Pages 10632-6

Yu BD, Hanson RD, Hess JL, Horning SE, Korsmeyer SJ

Abstract

Determinative events in vertebrate embryogenesis appear to require the continuous expression of spatial regulators such as the clustered homeobox genes. The mechanisms that govern long-term patterns of gene expression are not well understood. In Drosophila, active and silent states of developmentally regulated loci are maintained by trithorax and Polycomb group. We have examined the developmental role of a mammalian homolog of trx and putative oncogene, Mll. Knockout mice reveal that Mll is required for maintenance of gene expression early in embryogenesis. Downstream targets of Mll including Hoxa7 are activated appropriately in the absence of Mll but require Mll for sustaining their expression. The Mll-/- phenotype manifests later in development and is characterized by branchial arch dysplasia and aberrant segmental boundaries of spinal ganglia and somites. Thus, Mll represents an essential mechanism of transcriptional maintenance in mammalian development, which functions in multiple morphogenetic processes.

MeSH Terms
Animals DNA-Binding Proteins/genetics,metabolism Embryonic and Fetal Development Female Genes, Homeobox Histone-Lysine N-Methyltransferase Mice Mice, Knockout Morphogenesis Myeloid-Lymphoid Leukemia Protein Nervous System/embryology,metabolism Proto-Oncogenes Transcription Factors/genetics,metabolism
Chemicals
DNA-Binding Proteins Transcription Factors Myeloid-Lymphoid Leukemia Protein Histone-Lysine N-Methyltransferase Kmt2a protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yu B D
Howard Hughes Medical Institute, Division of Molecular Oncology, Departments of Medicine and Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hanson R D
Hess J L
Horning S E
Korsmeyer S J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.18.10632
Published
1998-09-01
Pages
10632-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC27946
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.18.10632 PMC Full Text View journal details
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