MEIS1 (Meis homeobox 1)

2013-01-01   Jorge Torres-Flores , Luis Felipe Jave-Suárez 


Atlas Image
MEIS1 locus is 2p14. The gene length is 137360 bp. In this region is located along with LOC729348, LOC100507073 and DNA methyltransferase 3A pseudogene 1 (DNMT3AP1).



MEIS1 (myeloid ecotropic viral insertion site 1) was identified in the mid-90s by Moskow and cols. (Moskow et al., 1995), as a viral integration site in murine myeloid leukemia cells. This gene encodes a transcription factor which belongs to the TALE-class (Three Amino-acid Loop Extension) of homeobox genes. TALE proteins are distinguished by the presence of three extra amino acids in the loop binding the first to the second alpha helix of the homeodomain (Holland et al., 2007). The MEIS1 gene has a length of 137360 base-pairs, and is constituted by 13 exons; there are four isoforms described to date that are produced by alternative splicing: the isoform Meis1a comprise all 13 exons and the Meis1b isoform lacks exon number 12 (Steelman et al., 1997; Sitwala et al., 2008). Meis1c lacks nucleotides encoding 49 amino acids (Val-162 to Gln-210), in murine embryos (Knoepfler et al., 1997). Furthermore, an isoform named Meis1d witch retains exon 12, but lacking exon number 8 has been described in murine colorectal cancer cells (Crist et al., 2011).
Atlas Image
Linear diagram of MEIS1 gene with their 13 exons (green boxes).


The MEIS1 gene has a length of 137360 base-pairs, encodes a homeodomain-containing protein. The gene is located on 2p14.


13 exons; mRNA linear (NM_002398.2) with 3198 bp.


No pseudogenes have been identified.



The MEIS1 protein consists of 390 amino acids and has a molecular weight of 43016 Daltons. Its expression has been found in hematopoietic stem cells, in murine fetal liver and also in other embryonic and fetal tissues. During embryogenesis, MEIS1 is actively involved in vascular development and hematopoiesis and after birth, is present in the bone marrow (Hisa et al., 2004; Azcoitia et al., 2005). MEIS1 expression is a necessary requirement to maintain cells in an undifferentiated and proliferative stage (Calvo et al., 2001).
Atlas Image
Diagram of MEIS1 interactions with other proteins. MEIS1 can be regulated directly or indirectly by other transcription factors, like HOXA9, PREP1 or CREB1 (yellow colored). Factors suggested to be downstream of MEIS1 are mostly involved in proliferation and differentiation (light blue colored).


390 amino acids. 43KDa. Presents homeodomain and MEIS1 recognizes the DNA binding sequence TGACAG (Shen et al., 1997).


MEIS1 is expressed physiologically in different tissues like bone marrow, hematopoietic stem cells, hindbrain, cerebellum, liver, pancreas islets, colon, smooth muscle, small intestine, eye, salivary gland, adrenal gland, endometrium, uterus, ovary, fetal lung, trachea and appendix. Additionally, MEIS1 is present in numerous cancers such as melanoma (Svingen and Tonissen, 2003), neuroblastoma (Geerts et al., 2005), pancreatic cancer (Tomoeda et al., 2011), colorectal cancer (Crist et al., 2011), breast cancer (Svingen and Tonissen, 2003), ovarian cancer (Crijns et al., 2007; Kelly et al., 2011), myeloid leukemia and lymphoblastic leukemia (Owens and Hawley, 2002). Cell lines IMR32, Jurkat and K562, also expresses MEIS1 (Jones et al., 2000; Spieker et al., 2001; Rosales-Aviña et al., 2011).


Nuclear (Dintilhac et al., 2005; Royo et al., 2012). In some cancers may also be cytoplasmic (Crijns et al., 2007).


Hematopoiesis and hepatic development are blocked in knockout mice for MEIS1, causing the death of specimens due to bleeding and liver hypoplasia (Hisa et al., 2004; Azcoitia et al., 2005). MEIS1 is regulated by various transcription factors such as HOXA7, HOXA9, PREP1 and CREB1; the latter two are also regulated by HOXA9 (Afonja et al., 2000; Thorsteindottir et al., 2001; Morgado et al., 2007; Hu et al., 2009). CREB proteins promote DNA binding of MEIS1 complexes and this collaboration could be favored by GSK3 (glycogen synthase kinase 3) (Wang et al., 2010).
Heterodimers of MEIS1 and PBX proteins (PBX1B or PBX2) activate platelet factor type 4 gene (PF4), demonstrating the involvement of MEIS1 in megakaryopoiesis (Okada et al., 2003).
Pax6 protein form heterodimers with Meis1 or Meis2, influencing the development of ocular structures such as lens and retina in vertebrates (Zhang et al., 2002; Heine et al., 2008). In Danio rerio, Meis1 regulates eph and Smad1, participating in the polarity of the visual pathway (Erickson et al., 2010); moreover, Bessa and cols., demonstrated that Meis1 regulates cyclin D1 and c-myc, both required for cell cycle (Bessa et al., 2008). Additionally, it has been described as a positive regulator of c-myb, a transcription factor with repressor functions (Dassé et al., 2012). The growth pattern of the zebrafish hindbrain is mediated through Pbx4; when this protein is suppressed in embryos, Meis1 plays a "rescue" role continuing the cerebellum development (Waskiewicz et al., 2001).
Dimeric complexes among MEIS1 and PBX1 upregulates SOX3 by binding to promoter region; SOX3 is a transcription factor involved in the final stages of cell development in the cerebral cortex and pituitary gland (Mojsin and Stevanovic , 2009).
In the embryonic pancreas, Pdx1 downregulates Meis1a, this depletion reduces significantly Keratin-19 (Krt19) mRNA expression. Krt19 is expressed in pancreatic ductal cells (von Burstin et al., 2010).
At the reproductive level, MEIS1 contributes to the endometrium development during the proliferative phase of the menstrual cycle, in both mice and humans (Sarno et al., 2005; Xu et al., 2008); and is expressed in the nuclei of granulosa cells (Ota et al., 2008).


Homologs of MEIS1 protein are highly conserved in different species.
Mus musculus: Meis1 (370 aminoacids)
Danio rerio: Meis1 (388aa)
Rattus norvegicus: Meis1 (390aa)
Gallus gallus: Meis1 (390aa)
Xenopus laevis: Meis1 (464aa)
Bos taurus: Meis1 (390aa)
Macaca mulatta: Meis1 (390aa)
Pan troglodytes: Meis homeobox 1 (390aa)
Drosophila melanogaster: homothorax isoform A (472aa), isoform B (471aa), isoform C (487aa), isoform d (457aa), isoform e (266aa), isoform f (266aa), isoform g (218aa), isoform h (458aa).

Implicated in

Entity name
High levels of MEIS1 in CD34+ hematopoietic cells are related with suppression of differentiation and promotion of proliferation (Abramovich et al., 2005). MEIS1 protein is overexpressed in bone marrow cells isolated from lymphoblastic and myeloid leukemia; this overexpression prevents the cell to respond to granulocyte-colony stimulating factor (G-CSF), an inducer of terminal differentiation (Calvo et al., 2001). Further, MEIS1 accelerates the leukemic process in cells expressing HOXA7, HOXA9 or HOXB3 (Thorsteindottir et al., 2001; Morgado et al., 2007; Wong et al., 2007). Additionally, MEIS1 unregulate FLT3 expression, promoting the formation of protein complexes with NUP98-HOXA10 and NUP98-HOXD13 and increasing the affinity of Homeobox proteins to bind DNA (Palmqvist et al., 2006). Interestingly, HOXA9 also upregulates FLT3 expression (Gwin et al., 2010). The co-expression of NUP98-HOXA9 complexes with Meis1 accelerates the transformation to acute myeloid leukemia (Kroon et al., 2001). HOXA9 and MEIS1 can repeal caspase-mediated apoptosis (Wermuth and Buchberg, 2005). MEIS1 overexpression is a poor prognosis marker in patients with leukemia (Diaz-Blanco et al., 2007). Down-modulation of MEIS1 by RNA interference produces a lower leukemic cell proliferation rate; this effect is more pronounced in K562 myeloid cell line than Jurkat lymphoblastic cell line. Interestingly, K562 expresses more MEIS1 than Jurkat, possibly because the cells have trisomy 2, and MEIS1 locus in 2p14. Silenced-MEIS1 Jurkat cells exhibit increased survival after exposure to etoposide (Rosales-Aviña et al., 2011).
Atlas Image
MEIS1 is present from the earliest stages of hematopoiesis. HSCP: Hematopoietic Stem Cell Proliferative, HSC: Hematopoietic Stem Cell, LPC: Lymphoid Precursor Cell, MPC: Myeloid Precursor Cell (partial diagram).
Entity name
Prostate cancer
Prostate cancer is related to failure of androgen receptor pathway; however, MEIS1 deregulation is also implicated. Paradoxically unlike leukemias, in prostate cancer the opposite occurs, elevated levels of Meis1 are highly associated with improved survival. In fact expression of Meis1 is higher in prostatic normal tissue than in prostate cancer tissue; this decreased expression plays a role in tumor initiation and progression. Not only decreased Meis1 is related to poor prognosis, loss of other proteins TALE class (Meis2 and Pbx1) also impacts life span (Chen et al., 2012).
Entity name
Pancreas cancer
Meis1 regulated the expression of mitochondrial genes by binding to the H-strand mitochondrial promoter region. In knocked down pancreatic cancer cells, decreases mitochondrial gene expression such as MT-CO1, MT-CO2, MT-CO3 (mitochondrial-cytochrome c oxidase subunits 1, 2 and 3, respectively), ATP synthase 6, ATP synthase 8, and multiple NADH-ubiquinone oxidoreductase chains. These findings have not been observed with low levels of other proteins TALE-class like PBX1 or PBX2 (Tomoeda et al., 2011).
Entity name
Endometrial and ovarian cancer
MEIS1 is highly expressed in endometrial and ovarian carcinomas. It has been demonstrated that in the normal endometrium this protein is expressed in early proliferative glandular epithelium, and after exposure of the ovarian surface epithelium cell line MCV152 to follicle-stimulating hormone (FSH) MEIS1 expression is elevated; the overexpression increases cellular proliferation (Ji et al., 2004; Sarno et al., 2005). Apparently MEIS1 expression is associated with resistance to cisplatin, a first-line chemotherapeutic agent (Crijns et al., 2007).
Entity name
Restless legs syndrome
The presence of the rs2300478 polymorphism in MEIS1 has been associated with high susceptibility to Restless Legs Syndrome (RLS) (Winkelmann et al., 2007), an autosomal dominant disorder characterized by irresistible desire to move the legs, presence of paresthesias and dysesthesias, decreased iron content in the substantia nigra, and abnormal levels of ferritin and transferrin in cerebrospinal fluid. Samples of lymphoblastic cells and cerebral tissue of RLS patients reveals subexpression of MEIS1 (Xiong et al., 2009).


Pubmed IDLast YearTitleAuthors
159587032005Hox genes: from leukemia to hematopoietic stem cell expansion.Abramovich C et al
109962032000MEIS1 and HOXA7 genes in human acute myeloid leukemia.Afonja O et al
158825752005The homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo.Azcoitia V et al
182161752008meis1 regulates cyclin D1 and c-myc expression, and controls the proliferation of the multipotent cells in the early developing zebrafish eye.Bessa J et al
116876162001Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: potential mechanisms of cooperativity with Hoxa9 in myeloid leukemia.Calvo KR et al
227233712012Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression.Chen JL et al
179499702007MEIS and PBX homeobox proteins in ovarian cancer.Crijns AP et al
218581982011A conserved tissue-specific homeodomain-less isoform of MEIS1 is downregulated in colorectal cancer.Crist RC et al
228299782012Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells.Dassé E et al
172520122007Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase.Diaz-Blanco E et al
161729812005PBX1 intracellular localization is independent of MEIS1 in epithelial cells of the developing female genital tract.Dintilhac A et al
208099322010Meis1 specifies positional information in the retina and tectum to organize the zebrafish visual system.Erickson T et al
159191492005MEIS homeobox genes in neuroblastoma.Geerts D et al
209719282010Hoxa9 regulates Flt3 in lymphohematopoietic progenitors.Gwin K et al
182161742008Evidence for an evolutionary conserved role of homothorax/Meis1/2 during vertebrate retina development.Heine P et al
147139502004Hematopoietic, angiogenic and eye defects in Meis1 mutant animals.Hisa T et al
179634892007Classification and nomenclature of all human homeobox genes.Holland PW et al
196202872009HOXA9 modulates its oncogenic partner Meis1 to influence normal hematopoiesis.Hu YL et al
153863762004Follicle stimulating hormone-induced growth promotion and gene expression profiles on ovarian surface epithelial cells.Ji Q et al
110943112000The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines.Jones TA et al
219063072011HOX genes in ovarian cancer.Kelly ZL et al
94056511997Meis1 and pKnox1 bind DNA cooperatively with Pbx1 utilizing an interaction surface disrupted in oncoprotein E2a-Pbx1.Knoepfler PS et al
111577422001NUP98-HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice.Kroon E et al
197995672009PBX1 and MEIS1 up-regulate SOX3 gene expression by direct interaction with a consensus binding site within the basal promoter region.Mojsin M et al
172023142007Flt3 is dispensable to the Hoxa9/Meis1 leukemogenic cooperation.Morgado E et al
75656941995Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.Moskow JJ et al
126098492003Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene.Okada Y et al
189736872008HOX cofactors expression and regulation in the human ovary.Ota T et al
123518082002HOX and non-HOX homeobox genes in leukemic hematopoiesis.Owens BM et al
168613512006The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia.Palmqvist L et al
221852992011MEIS1, PREP1, and PBX4 are differentially expressed in acute lymphoblastic leukemia: association of MEIS1 expression with higher proliferation and chemotherapy resistance.Rosales-Aviña JA et al
224482562012Identification and analysis of conserved cis-regulatory regions of the MEIS1 gene.Royo JL et al
154944612005HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: formation of multimeric complexes on HOXA10 target genes.Sarno JL et al
93434071997AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins.Shen WF et al
187876822008HOX proteins and leukemia.Sitwala KV et al
111618152001The MEIS1 oncogene is highly expressed in neuroblastoma and amplified in cell line IMR32.Spieker N et al
90496321997Identification of a conserved family of Meis1-related homeobox genes.Steelman S et al
146143182003Altered HOX gene expression in human skin and breast cancer cells.Svingen T et al
111131972001Defining roles for HOX and MEIS1 genes in induction of acute myeloid leukemia.Thorsteinsdottir U et al
217032372011Role of Meis1 in mitochondrial gene transcription of pancreatic cancer cells.Tomoeda M et al
205417042010GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis.Wang Z et al
116846522001Zebrafish Meis functions to stabilize Pbx proteins and regulate hindbrain patterning.Waskiewicz AJ et al
154797232005Meis1-mediated apoptosis is caspase dependent and can be suppressed by coexpression of HoxA9 in murine and human cell lines.Wermuth PJ et al
176377802007Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.Winkelmann J et al
179427072007Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential.Wong P et al
191267762009MEIS1 intronic risk haplotype associated with restless legs syndrome affects its mRNA and protein expression levels.Xiong L et al
184080192008Myeloid ecotropic viral integration site 1 (MEIS) 1 involvement in embryonic implantation.Xu B et al
121833642002Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis.Zhang X et al
208088192010The pancreatic and duodenal homeobox protein PDX-1 regulates the ductal specific keratin 19 through the degradation of MEIS1 and DNA binding.von Burstin J et al

Other Information

Locus ID:

NCBI: 4211
MIM: 601739
HGNC: 7000
Ensembl: ENSG00000143995


dbSNP: 4211
ClinVar: 4211
TCGA: ENSG00000143995


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Developmental BiologyREACTOMER-HSA-1266738
Activation of HOX genes during differentiationREACTOMER-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesisREACTOMER-HSA-5617472

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
200620602010Genome-wide association study of PR interval.185
176377802007Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.156
147017352004Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization.133
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
223537102012miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia.70
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
205417042010GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis.54
191095632009A role for MEIS1 in MLL-fusion gene leukemia.45
191267762009MEIS1 intronic risk haplotype associated with restless legs syndrome affects its mRNA and protein expression levels.33


Jorge Torres-Flores ; Luis Felipe Jave-Suárez

MEIS1 (Meis homeobox 1)

Atlas Genet Cytogenet Oncol Haematol. 2013-01-01

Online version: