Myeloid-specific gene expression

Abstract

The mononuclear phagocytes are recruited from bone marrow precursors to most tissues of the body, particularly during inflammation or immune stimulation. This combination of accessibility as stem cells and heterogenity of tissue locations makes the myeloid cell potentially important as a carrier of therapeutic agents. Understanding the regulation of transcription in myeloid cells is necessary for any future design of tissue-specific gene targeting vectors, particularly if there are inherent size limitations. Identified members of the C/EBP, Runt/PEBP2/CBF, and Ets families of transcription factors are critical for myeloid-specific gene expression and may have myeloid-restricted expression or myeloid-specific regulation in the hematopoietic system. AP-1, Sp1, and Myb appear to be important for myeloid-restricted expression in some cases. In addition, factors involved in the up-regulation of the level of gene expression when macrophages are activated by agents such as interferon-gamma and bacterial products have been identified. Some of the sequences to which these transcription factors bind in myeloid-restricted genes have been tested in cell lines and in transgenic mice and it is now possible to make an attempt to describe the characteristics of a myeloid-specific promoter.

C/EBPδ and STAT-1 Are Required for TLR8 Transcriptional Activity

“…Coherently, we did not detect any TLR8 transcriptional activity in non-myeloid cells such as HUH-7 or HEK cell lines. Moreover, TLR8 promoter sequence appeared to share common features with other myeloid-specific promoters (16,40) such as the lack of a TATA box, the presence of C/EBP-responsive elements, and purine-rich sequence motifs that are recognized by the Ets family. Regarding the role of Ets family members in TLR8 transcriptional regulation, we observed that overexpression of SpiC, SpiB, or Spi1 (PU.1) did not affect TLR8 promoter activity.…”

AML-1, PU.1, and Sp3 regulate expression of human bactericidal/permeability-increasing protein

“…Sp1 is often involved in the regulation of promoters that lack a TATA-box, [48] a characteristic sign of several promoters for neutrophil granule proteins (reviewed in [49]). It is unclear whether the promoter for BPI contains a functional TATA-box.…”

Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors

“…Fes act Activates STAT3 and C/EBP-␣ but Not PU.1-Since Fes act was able to induce granulocyte differentiation, we examined whether this kinase activated transcription factors that are important for myeloid development (1). To this end, we carried out EMSA of nuclear extracts from Fes act -infected 32D cells.…”

“…The differentiation of myeloid progenitors into monocytemacrophages and granulocytes is regulated by the combined action of microenvironmental signals and lineage-specific transcription factors (1). One of the transcription factors involved in granulocytic differentiation is CCAAT/enhancer-binding protein (C/EBP) 1 ␣: the promoters of G-CSFR and other granulocytic genes contain binding sites for C/EBP-␣ (1, 2); C/EBP-␣ knockout mice have no mature neutrophils or eosinophils (3); and conditional expression of C/EBP-␣ alone can induce granulocytic differentiation in U937, HL-60, and 32D cells (4,5).…”