Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 40

2.4.1.4 Inhibitor of DNA Binding

Inhibitor of DNA binding ID2 modulates function of B- and T-cell lineages. It is
required for the development of mature natural killer cells. It impedes E-protein
activity. NK-cell lineage commitment can be controlled by ID2 or ID3 (bHLHb26
and bHLHb25) [ 70 ]. Protein bHLHb26 links to anaphase promoting complex, or
cyclosome, and this ubiquitin ligase promotes its degradation.

2.4.1.5 bHLHa17 and Runx1 Transcription Factors

Tissue-specific basic helix-loop-helix transcription factor bHLHa17, or T-cell
acute lymphocytic leukemia protein TAL1, 39 that upregulates stem cell factor
receptor is needed for the establishment of hemogenic endothelium. On the other
hand, transcription factor Runx1 40 is required for the formation of clusters of
hematopoietic stem cells from bipotential precursors of hemogenic endothelial
cells [ 73 ]. 41 However, Runx1 is dispensable in cells that express Vav1 guanine
nucleotide-exchange factor, one of the first pan-hematopoietic genes expressed
in hematopoietic stem cells. Therefore, Runx1 requirement ceases in Vav1

+

hematopoietic stem cells.
Hemodynamic stress increases the expression of Runx1 in CD41 +

hematopoietic progenitor cells and their hematopoietic colony-forming potential
[ 74 ]. 42 Nitric oxide that is involved in mechanical stress signaling promotes
hematopoietic potential in vivo.

+ ,SCFR

39 Transcription factor bHLHa17 is coexpressed with stem cell factor receptor in hematopoietic
progenitors. Factor bHLHa17 constitutes a nucleation factor for a multifactorial complex with
LIM-only protein-2 (LMO2; a.k.a. rhombotin-like protein-1, rhombotin-2, and T-cell translocation
protein TTG2), GATA1, GATA2, bHLHb21, and LIM domain-binding protein LDB1 (a.k.a. C-
terminal LIM domain-binding protein CLIM2 and nuclear LIM interactor [NLI]) that specifically
enhances SCFR promoter activity via Specificity protein SP1 [ 71 ]. It also forms heterodimers
with bHLHb20 and bHLHb21 factors. Activation of the TAL1 gene is the most frequent gain-
of-function mutation in T-cell acute lymphoblastic leukemia. Factor bHLHa17 acts as both an
activator and repressor of transcription. The Sin3a-HDAC1 corepressor complex interacts with
bHLHa17 to restrict its function in erythroid differentiation [ 72 ].
40 Runt-related transcription factor Runx1 is also termed Acute myeloid leukemia AML1.
41 Vascular regions that generate hematopoietic stem cell in mice comprise endothelia of the dorsal
aorta and vitelline and umbilical arteries, as well as yolk sac blood islands and distal allantois and
chorion that are precursors of the placenta. These independent sites constitute the conceptus.
42 Mechanical forces contribute to the regulation of the developing cardiovascular system in
embryos. After initiation of the heartbeat, cells lining the dorsal aorta, placental vessels, and
umbilical and vitelline arteries initiate expression of the transcription factor Runx1 [ 74 ].