Table 2.
Possible regulators of gene regulation during commitment and gametocytogenesisa
| Gene | Evidence | Other notes |
|---|---|---|
| Epigenetic factors | ||
| ISWI (PF3D7_0624600/PFF1185w) | Upregulated in AP2-G+ cells (both AP2-G-DD and NF54) (60) and upregulated in response to LysoPC depletion (8) | Localizes to central area of nucleus (79) |
| LSD2 (PF3D7_0801900/PF08_0133) | Upregulated in AP2-G+ cells (both AP2-G-DD and NF54) (60) | |
| Gametocyte development 1/Gdv1 (PF3D7_0935400/PFI1710w) | A naturally occurring deletion leads to loss of gametocyte formation, and overexpression leads to increased gametocytogenesis (23, 24) | |
| Histone deacetylase 2/Hda2 (PF3D7_1008000/PF10_0078) | Knockdown leads to derepression of the ap2-g locus and increased commitment (18) | |
| SNF2L (PF3D7_1104200/PF11_0053) | Upregulated in AP2-G+ cells (both AP2-G-DD and NF54) (60) and upregulated in response to LysoPC depletion (8) | |
| Heterochromatin protein 1/HP1 (PF3D7_1220900/PFL1005c) | HP1 is enriched at the ap2-g locus (27, 28), and knockdown leads to derepression of the locus and increased commitment (6) | |
| Histone deacetylase 1/Hda1 (PF3D7_1472200/PF14_0690) | Upregulated in AP2-G+ cells (both AP2-G-DD and NF54) (60) | |
| Transcription factors | ||
| SIP2 (PF3D7_0604100/PFF0200c) | Upregulated in AP2-G+ cells (AP2-G-DD only) (60) and transcript stabilized in gametocytes (57) | Involved in heterochromatin formation (26) |
| PF3D7_0613800/PFF0670w | Upregulated in AP2-G+ cells (NF54 only) (60) and upregulated in response to LysoPC depletion (8) | |
| PF3D7_1139300/PF11_0404 | Upregulated in AP2-G+ cells (both AP2-G-DD and NF54) (60) | |
| PF3D7_1143100/PF11_0442 (PbAP2-O) | Upregulated/stabilized in gametocytes (45, 57) | Disruption results in strongly reduced numbers of ookinetes (P. berghei) (52, 87) |
| PF3D7_1222400/PFL1075w | Upregulated in AP2-G+ cells (both AP2-G-DD and NF54) (60) and upregulated in response to LysoPC depletion (8) | |
| PF3D7_1222600/PFL1085w (PfAP2-G, PbAP2-G, PyAP2-G) | Naturally occurring mutations, disruption, or knockdown prevents gametocyte formation (37, 71, 88); overexpression leads to increased gametocyte commitment (39) | |
| PF3D7_1317200/PF13_0097 (PyAP2-G3) | Insertion of the piggyBac transposon in the gene (P. falciparum) or deletion (P. yoelii) leads to reduced gametocyte formation (34, 88) | |
| PF3D7_1408200/PF14_0079(PbAP2-G2, PyAP2-G2) | Disruption leads to greatly reduced gametocyte numbers (in P. berghei and P. yoelii) (71, 85, 88) | |
| PF3D7_1429200/PF14_0271 | Upregulated in gametocytes (45) | Disruption is possible, but no phenotype has been described (46) |
| AP2-exp (PF3D7_1466400/PF14_0633, PbAP2-SP) | Upregulated in AP2-G+ cells (AP2-G-DD only) (60) | Involved in regulating clonally variant gene families (P. falciparum) (48), required for sporozoite formation (P. berghei) (52, 86) |
| Posttranscriptional regulators | ||
| Puf2 (PF3D7_0417100/PFD0825c) | Disruption leads to increased numbers of gametocytes, as Puf2 translationally represses gametocyte transcripts (50, 51) | |
| Puf1 (PF3D7_0518700/PFE0935c) | Disruption leads to decreased numbers of mature gametocytes (66) | |
| Alba4(PF3D7_1347500/MAL13P1.237) | Disruption leads to fewer centers of movement (i.e., less exflagellation) (in P. yoelii) (53) | |
Abbreviation: LysoPC, lysophosphatidylcholine.
a
Genes shown either have a gametocyte phenotype upon depletion or disruption or are upregulated in AP2-G-expressing cells or gametocytes (60). Other studies that indirectly influence expression of ap2-g also identify possible regulators (6, 8, 18), but because these reports are confounded by AP2-G-independent effects they are not shown here.