Transcriptional regulation of ILT family receptors.
Ig-like transcripts (ILT/leukocyte Ig-like receptor/monocyte/macrophage Ig-like receptor or CD85) are encoded on human chromosome 19q13.4, designated the human leukocyte receptor complex, and are predominantly expressed on myeloid lineage cells. We investigated the transcriptional regulation of ILT1, ILT2, and ILT4 genes to elucidate control mechanisms operating on the specific expression of ILT receptors. Inhibitory ILT2 and ILT4 both have a similar genomic structure, in which the approximately 160-bp 5'-flanking regions function as core promoters with critically important PU.1 binding sites. However, an Sp1 family-binding GC-box is more influential in trans-activation of ILT2 than ILT4. Additionally, ILT4 transcription is tightly regulated by chromatin modifications accompanied by histone acetylation, which strictly controls expression within myeloid lineage cells. Activating ILT1 carries a core promoter corresponding to the intronic region of ILT2 and ILT4, where PU.1 and Runx1 binding sites are essential, but a downstream heat shock element also augments promoter activity. Thus, each ILT is regulated by a distinct transcriptional mechanism, although PU.1 acts as a common trans-acting factor. We also found that human CMV infection strongly trans-activates inhibitory ILT2 and ILT4 genes through the expression of immediate-early proteins.
Nakajima
Hideo
H
Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi, Japan. hideonak@nils.go.jp
Asai
Azusa
A
Okada
Aki
A
Ping
Lin
L
Hamajima
Fumiyasu
F
Sata
Tetsutaro
T
Isobe
Kenichi
K
D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D005091:Exons; D005786:Gene Expression Regulation / Q000276:immunology; D017781:Genes, Immediate-Early / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020298:U937 Cells; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D002843:Chromatin; C105298:LILRA2 protein, human; C105299:LILRB1 protein, human; C491341:LILRB2 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011971:Receptors, Immunologic