RUNX3 negatively regulates CD36 expression in myeloid cell lines.
CD36 is a member of the scavenger receptor type B family implicated in the binding of lipoproteins, phosphatidylserine, thrombospondin-1, and the uptake of long-chain fatty acids. On mononuclear phagocytes, recognition of apoptotic cells by CD36 contributes to peripheral tolerance and prevention of autoimmunity by impairing dendritic cell (DC) maturation. Besides, CD36 acts as a coreceptor with TLR2/6 for sensing microbial diacylglycerides, and its deficiency leads to increased susceptibility to Staphylococcus aureus infections. The RUNX3 transcription factor participates in reprogramming DC transcription after pathogen recognition, and its defective expression leads to abnormally accelerated DC maturation. We present evidence that CD36 expression is negatively regulated by the RUNX3 transcription factor during myeloid cell differentiation and activation. In molecular terms, RUNX3 impairs the activity of the proximal regulatory region of the CD36 gene in myeloid cells through in vitro recognition of two functional RUNX-binding elements. Moreover, RUNX3 occupies the CD36 gene proximal regulatory region in vivo, and its overexpression in myeloid cells results in drastically diminished CD36 expression. The down-regulation of CD36 expression by RUNX3 implies that this transcription factor could impair harmful autoimmune responses by contributing to the loss of pathogen- and apoptotic cell-recognition capabilities by mature DCs.
Puig-Kröger
Amaya
A
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas (CSIC), Ramiro de Maeztu 9, Madrid 28040, Spain.
Domínguez-Soto
Angeles
A
Martínez-Muñoz
Laura
L
Serrano-Gómez
Diego
D
Lopez-Bravo
María
M
Sierra-Filardi
Elena
E
Fernández-Ruiz
Elena
E
Ruiz-Velasco
Natividad
N
Ardavín
Carlos
C
Groner
Yoram
Y
Tandon
Narendra
N
Corbí
Angel L
AL
Vega
Miguel A
MA
D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation / Q000276:immunology; D002522:Chlorocebus aethiops; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D020014:K562 Cells; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020298:U937 Cells
D018955:CD36 Antigens; D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human