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. 2005 Feb;25(4):1215-27.
doi: 10.1128/MCB.25.4.1215-1227.2005.

GATA1 function, a paradigm for transcription factors in hematopoiesis

Rita Ferreira  1 , Kinuko Ohneda, Masayuki Yamamoto, Sjaak Philipsen
Affiliations

GATA1 function, a paradigm for transcription factors in hematopoiesis

Rita Ferreira et al. Mol Cell Biol. 2005 Feb.
No abstract available

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Figures

FIG. 1.
FIG. 1.
The hematopoietic tree. Schematic representation of the main lineage commitment steps in hematopoiesis. The hematopoietic stem cell (HSC) is the basis of the hematopoietic hierarchy and gives rise to multilineage progenitors (MLP), which can differentiate into all the hematopoietic lineages. MLPs become lineage restricted to the lymphoid and myeloid lineages in the common lymphoid progenitor (CLP) and common myeloid progenitor (CMP), respectively. CLPs can give rise exclusively to B and T cells, while CMPs can give rise to megakaryocyte-erythrocyte progenitors (MEP) and granulocyte-monocyte progenitors (GMP). Alternatively, it is also believed that the first lineage commitment separates myeloid and erythroid potential, in the CMP, from myeloid-lymphoid potential, in the common myeloid lymphoid progenitor (CMLP). CMLPs can than further differentiate in B cells, T cells, and GMPs (dashed line). Hematopoietic GATA factors and GATA1 cofactors relevant for the development of particular hematopoietic lineages are indicated.
FIG. 2.
FIG. 2.
The hematopoietic GATA transcription factors. A schematic representation of the mouse hematopoietic GATA proteins is shown. The highly conserved region comprising the zinc-finger domains is indicated in black; the regions between the zinc-chelating cysteines are highlighted. The N-terminal activation domain (aa 1 to 83 of GATA1) and the known sites modified by acetylation (A), phosphorylation (P), or SUMOylation (S) are indicated by numbers. Numbering starts at the first methionine of the proteins.
FIG. 3.
FIG. 3.
Three-dimensional (3D) representation of the C-terminal finger of chicken GATA1 bound to DNA. The figure was prepared using the file 2GAT.pdb (101) and Swiss-pdb viewer software (http://www.expasy.org/spdbv/) (33). The 3D structure of the 66-aa peptide is displayed as a ribbon (red). The sequence of this peptide is >90% identical to residues 252 to 317 in human and mouse GATA1. Side chains of the four Cys residues (yellow) chelating the zinc atom (orange sphere), one residue of the phosphorylation site (S310; purple), and two residues of the critical acetylation site (K314 and K315; dark blue) are shown. Numbering is according to the homologous residues in human and mouse GATA1. DNA residues (5′-TTTATCTG-3′ and 5′-CAGATAAA-3′) are labeled and color coded. The C-terminal extension of the zinc-finger makes extensive contacts with the minor groove of the DNA (78). The side chains of S310, K314, and K315 point away from the DNA, suggesting that they might be accessible to other proteins when GATA1 is bound to DNA.
FIG. 4.
FIG. 4.
The mouse GATA1 locus. The exon-intron structure of the mouse GATA1 gene is displayed, and the positions of known regulatory elements (bars) and hematopoietic DNase I HS sites (red arrows) (36, 63) are shown. Translated sequences are in dark purple. IT, testis-specific exon 1; IE, hematopoietic-specific exon 1; G1TAR, GATA1 testis-activating region; G1HE, GATA1 hematopoietic enhancer.
FIG. 5.
FIG. 5.
Model for the dynamic regulation of GATA1 and GATA2 activity during erythropoiesis. GATA2 is expressed at high levels in early erythroid progenitors. When GATA1 is activated, GATA2 is repressed and GATA1 levels increase, possibly through cross-talk between GATA1 and GATA2. During terminal erythroid differentiation, GATA1 is downregulated via an autonomous cell signaling mechanism that might involve death receptors and/or ligands.
FIG. 6.
FIG. 6.
Mutations in the N-terminal finger of GATA1 causing human disease. The figure was prepared using the file 1GNF.pdb (51) and Swiss-pdb viewer software (http://www.expasy.org/spdbv/) (33). The 3D structure of A201 to P240 of human and mouse GATA1 is displayed as a ribbon (pink); the zinc atom is displayed as an orange sphere. The positions of the zinc-chelating Cys residues on the ribbon are indicated in yellow; the positions of residues involved in the interaction with FOG-1 are in blue (23). Side chains are shown for the residues mutated in patients. Blue, the mutations V205 M (75), G208S (64), D218G (25), and D218Y (26) interfere with FOG-1 binding; red, the mutation R216Q (133) interferes with DNA binding.
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References

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