Table I.
Expression, Function, and Pathobiology of Mammalian KLF Family Proteins
| Name | Also known as | Expression pattern | Tissue function/disease association | Gene knockout phenotypes | References |
|---|---|---|---|---|---|
| KLF1 | EKLF (Erythroid Krüppel-like factor) | Erythroid cells, fetal liver, adult bone marrow and spleen | Erythropoiesis; megakaryocyte differentiation | Defective hematopoiesis and lethal β-thalassemia at E14.5 | (144, 311, 335) |
| KLF2 | LKLF (Lung Krüppel-like factor) | Lungs, erythroid cells, vascular endothelial cells, T lymphocytes, white adipose tissue | Erythropoiesis; regulator of hemodynamics; lung development; T cell survival, migration and trafficking; inhibitor of adipogenesis; important in generating induced-pluripotent stem (iPS) cells | Embryonic lethality due to compromised vessel integrity/rupture; delayed lung development; defective T-lymphocyte and adipocyte differentiation | (21, 51, 234, 235, 243, 295, 448, 464) |
| KLF3 | BKLF (Basic Krüppel-like factor) | Widely expressed; abundant in erythroid cells | Inhibits adipocyte differentiation | Decreased white adipose tissue | (95, 409) |
| KLF4 | GKLF (Gut-enriched Krüppel-like factor); EZF (Endothelial zinc finger protein) | Epithelia of gut, skin and lungs; endothelial cells; early precursor B cells | Intestinal epithelial homeostasis; tumor suppressor in colon cancer; oncogene in breast cancer and squamous cell carcinoma; promotes adipogenesis; critical factor in generating iPS cells | Perinatal lethal due to dehydration with skin barrier defect; abnormal differentiation of goblet cells in the colon | (151, 211, 272, 367, 415, 416, 433) |
| KLF5 | IKLF (Intestinal-enriched Krüppel-like factor); BTEB2 (Basic transcription element binding protein-2) | Enriched in gut epithelia; expressed in epidermis, vascular smooth muscle and white adipose tissue; also developing/perinatal skeleton and lung | Intestinal homeostasis; cardiac remodeling; lung maturation and morphogenesis; promotes adipogenesis; important in generating iPS cells; dysregulated expression in colon, breast, prostate cancer and other solid tumors | Embryonic lethal at E8.5; heterozygous and tissue-specific deletions show: reduced cardiac fibrosis and hypertrophy in response to stress, deficiencies in white adipose tissue development, skeletal growth retardation, defective perinatal lung morphogenesis; heterozygous deletion drastically reduces intestinal tumor formation in ApcMin mice and ApcMin/KRASV12 mice | (52, 57, 58, 89, 271, 272, 295, 298, 299, 318, 378, 379, 417, 423, 440) |
| KLF6 | ZF9 (Zinc-finger transcription factor-9); CPBP (Core promoter binding protein); GBF (G-box binding factor) | Strongly expressed in placenta and developing hindgut, heart, lung and kidney; adult endothelial cells, heart, liver, lung, kidney, intestine | Promotes vascular remodeling; stimulates adipogenesis; tumor suppressor in prostate cancer; silenced or mutated in a variety of other cancers | Embryonic lethal at E12.5, with reduced hematopoiesis and poor yolk sac vascularization | (13, 113, 135, 240, 267, 268, 305, 389) |
| KLF7 | UKLF (Ubiquitous Krüppel-like factor) | High expression in brain and spinal cord; expressed in developing central and peripheral nervous systems; | Inhibits adipocyte differentiation; single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes | Neonatal lethality by P3 associated with defects in neurite outgrowth and axonal misprojection | (209, 239, 241, 268) |
| KLF8 | - | Low, ubiquitous expression | Elevated in ovarian and other human cancers | - | (432, 445) |
| KLF9 | BTEB (Basic transcription element-binding protein) | Broadly expressed; high in developing brain, thymus, epithelia and smooth muscle of gut and bladder | Endocrine-responsive cancers, including endometrial cancer | Normal lifespan, but specific behavioral abnormalities; subfertility and parturition defects in females; shorter small intestinal villi | (265, 290, 383–385) |
| KLF10 | TIEG1 (TGF-inducible gene-1); mGIF (murine glial cell-derived neurotrophic factor (GDNF)-inducible factor) | Broadly expressed, including pancreas, kidney, lung, brain, liver, heart and testis | T eg cell differentiation and T cell activation; bone development; SNPs associated with volumetric bone mineral density; implicated in breast cancer | Normal lifespan, but osteopenia in females; cardiac hypertrophy in males; defects in structure and healing of tendons | (26, 50, 175, 343, 405, 406, 468, 476) |
| KLF11 | FKLF (Fetal-like globin gene-activating Krüppel-like factor); TIEG2 (TGF- -inducible gene-2); MODY7 (Maturity-onset diabetes of the young-7) | Erythroid cells in fetal liver; ubiquitous in adult including pancreas | Tumor suppressor in pancreatic cancer; variants associated with early-onset type 2 diabetes | Normal development, lifespan, fertility | (12, 43, 91, 122, 308, 396) |
| KLF12 | AP-2rep (Activator protein-2α repressor) | Expression in developing brain and kidney; adult kidney, very low in liver and lung | Implicated in breast and gastric cancer | - | (192, 296, 353, 408) |
| KFL13 | BTEB3 (Basic transcription element-binding protein-3); FKLF2 (Fetal -like globin gene-activating Krüppel-like factor-2); RFLAT-1 (RANTES factor of late-activated T lymphocytes 1) | Broadly expressed; high temporal expression in developing heart, brain, thymus, epidermis, gut and bladder epithelia | Cardiac development; B and T cell development | Splenomegaly and aberrant erythroblast differentiation; abnormal T and B cell development; increased T cell survival | (157, 242, 265, 322, 506) |
| KFL14 | - | Ubiquitous | Variants associated with basal cell carcinoma | - | (328, 364, 401) |
| KLF15 | KKLF (Kidney-enriched Krüppel-like factor) | Low cardiac expression during development; adult kidney, liver, pancreas, heart, skeletal muscle, lung, ovary | Regulator of gluconeogenesis; negative regulator of cardiac hypertrophy and fibrosis | Normal viability, fertility; exaggerated cardiac fibrosis and hypertrophy in response to stress; defective amino acid metabolism resulting in hypoglycemia | (134, 159, 428, 441) |
| KLF16 | BTEB4 (Basic transcription element-binding protein-4); DRRF (Dopamine receptor regulating factor) | Highly expressed in regions of developing brain; lower expression in thymus, duodenum, kidney, liver, heart, bladder and lung | - | - | (99, 191) |
| KLF17 | Zfp393 (Zinc finger protein 393) | Spermatids and oocytes | - | - | (431, 471) |