Molecular switches involving homeodomain proteins, HOXA10 and RUNX2 regulate osteoblastogenesis.
The osteoinductive BMP2 signal facilitates commitment to the osteoblast phenotype by inducing several classes of early response genes. Among these are bone-related HOX factors, homeodomain, RUNX and OSTERIX proteins. Here we demonstrate molecular events among BMP2-induced transcription factors that constitute a network of molecular switches on promoters of bone-related genes to coordinate their temporal expression during cellular differentiation. Our studies provide evidence for (1) selective association of HOXA10, MSX2, DLX3 and DLX5 homeodomain transcription factors on Runx2 and OC genes at stages of osteoblast maturation as well as (2) participation of these factors with RUNX2 in chromatin remodeling of bone-specific genes for repression, activation and attenuation of transcription. These findings reveal the requirement for multiple levels of control for the appropriate timing of osteoblast-related gene expression.
Hassan
Mohammad Q
MQ
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Mass. 01655, USA.
Saini
Sharanjot
S
Gordon
Jonathan A R
JA
van Wijnen
Andre J
AJ
Montecino
Martin
M
Stein
Janet L
JL
Stein
Gary S
GS
Lian
Jane B
JB
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005812:Genes, Switch; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D051381:Rats
D002843:Chromatin; D050659:Core Binding Factor Alpha 1 Subunit; C534680:HOXA10 protein, rat; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins