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).

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).

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).