Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 37

Tabl e 2. 7. E-protein-dependent genes in B and T lymphocytes, plasmacytoid dendritic cells and
their multipotent progenitors ( Part 1 ; Source: [ 70 ]; IGA: Ig -type of immunoglobulin heavy

(IgH)-chain gene, or CD79A; IGI: preB-lymphocyte (VPREB1) Ig

α

ι -chain gene, or CD179A; IGK:

Ig κ -type of immunoglobulin light (IgL) chains ( κ ) of immunoglobulin light (IgL); IGLL1: Ig λ -

like polypeptide-1, a.k.a. CD179B, IGL1, IGL5 [that encodes Ig 5], and VPREB2; SPI1: spleen

focus-forming virus [SFFV] proviral integration proto-oncogene product; SPIb: SPI1-related
transcription factor; TCR

λ

). E proteins were initially identified by their ability
to bind to E-box sequences in B cells. E2A proteins control immunoglobulin gene transcription and
recombination, as they bind intronic enhancers of the IGH and IGK gene for proper rearrangement
of gene segments. E proteins maintain hematopoietic stem cell quiescence. They regulate the
transcription of many transcription factors and proteins, such as V(D)J recombination-activating
gene products RAG1 and RAG2; immunoglobulin heavy chain IgH6 [IgH of IgM]; preT-cell
receptor

β : T-cell receptor- β

]; early B-cell factor gene [EBF],
cell cycle regulators myelocytomatosis viral-related proto-oncogene NMYC (neuroblastoma-
derived MYC; a.k.a. MYCN and subclass-E basic helix-loop-helix protein bHLHe37) and CMYC
(or bHLHe39); messenger Notch-1 and its targets such as Hairy and enhancer of Split [HES1, or
subclass-B bHLHb39] and Deltex homolog-1; as well as plasmacytoid dendritic cell-associated
genes such as terminal deoxynucleotidyltransferase gene [Dntt] and CC-chemokine receptor
gene Ccr9; growth factor-independent gene Gfi1 for early T-cell development). They cooperate
with various transcription factors (e.g., interferon regulatory factor IRF4, Paired box protein
Pax5, SPI1, and Ikaros family zinc finger-containing protein IKZF1). E2A proteins regulate cell
cycle progression in hematopoietic stem cells, as they control expression of the CDKN1A and
CDKN1B genes (that encode cyclin-dependent kinase inhibitors CKI1a and CKI1b), of the Gfi1
gene (growth factor-independent-1 transcription repressor), and myeloproliferative leukemia virus
proto-oncogene (MPL) that encodes thrombopoietin receptor (TpoR). Transcription factors of the
E2A family that target the Rag1, Dntt, and Igh6 genes regulate multipotent progenitors for the
formation of common lymphoid progenitors.

α chain [pTCR α ]; interleukin-7 receptor α chain [Il7R α

Cell Cell-specific Specification and

type genes commitment factors

B lymphocyte IGA, IGI, IGK, IGLL1, NMYC EBF1

T lymphocyte deltex-1, Hes1, PTCRA, TCRB, Gfi1b Notch-1

Plasmacytoid Irf8 SPIb

Dendritic cell

Transcription factors of the E protein family together with ID proteins regulate
the transcription of many genes, as they operate in the development of many
lymphoid cell types and govern the earliest restriction events in lymphopoiesis
(Tables 2.7 and 2.8 ).

protein ZMYND2, acute myeloid leukemia AML1 (Runx1)-ETO fusion protein, and Sin3a
histone deacetylase complex subunit. The most frequent chromosomal translocation in acute
leukemia creates the Runx1-Runx1T1 fusion protein, which represses transcription via Runx1
and immortalizes hematopoietic progenitor cells. On the other hand, heterodimers made up of
E and ID proteins fail to activate gene transcription. E-box CANNTG (N denotes any nucleotide)
sequences belong to the enhancer regions of genes that encode immunoglobulin heavy (IgH) and
κ κ

) of immunoglobulin light (IgL) chain. In T lymphocytes, unlike B lymphocytes, E-box
binding complexes contain high amounts of both bHLHb20 and bHLHb21 factors.

chain (Ig