* 602295

FORKHEAD BOX A3; FOXA3


Alternative titles; symbols

HEPATOCYTE NUCLEAR FACTOR 3-GAMMA; HNF3G


HGNC Approved Gene Symbol: FOXA3

Cytogenetic location: 19q13.32     Genomic coordinates (GRCh38): 19:45,864,326-45,873,797 (from NCBI)


TEXT

Description

The hepatocyte nuclear factors (see HNF1A, 142410) are transcriptional activators for liver-specific transcripts such as albumin and transthyretin. The HNF3 family, including HNF3A (602294), HNF3B (600288), and HNF3G, are members of the forkhead class of DNA-binding proteins (Kaestner et al., 1994).


Cloning and Expression

Kaestner et al. (1994) cloned the mouse Hnf3a, Hnf3b, and Hnf3g genes. The genes encode polypeptides of 468, 459, and 354 amino acids, respectively. Both Hnf3a and Hnf3b are expressed in tissues of endodermal origin, i.e., stomach, intestines, liver, and lung, whereas Hnf3g is more extensively expressed, being present additionally in ovary, testis, heart, and adipose tissue, but missing from lung.


Mapping

Mincheva et al. (1997) used fluorescence in situ hybridization to map the HNF3G gene to chromosome 19q13.2-q13.4. By analysis of RFLPs in interspecific backcross mice, Avraham et al. (1992) mapped the mouse Hnf3-gamma gene to the proximal region of chromosome 7.


Gene Function

Huang et al. (2011) demonstrated the direct induction of functional hepatocyte-like (induced hepatocyte, iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4 (600576), Hnf1-alpha (142410), and Foxa3 and inactivation of p19(Arf) (600160). iHep cells showed typical epithelial morphology, expressed hepatic genes, and acquired hepatocyte functions. Notably, transplanted iHep cells repopulated the livers of fumarylacetoacetate hydrolase-deficient (Fah-null; see 613871) mice and rescued almost half of recipients from death by restoring liver functions.

Sekiya and Suzuki (2011) screened the effects of 12 candidate factors to identify 3 specific combinations of 2 transcription factors, comprising Hnf4-alpha (600281) plus Foxa1 (602294), Foxa2 (600288), or Foxa3, that can convert mouse embryonic and adult fibroblasts into cells (iHep) that closely resemble hepatocytes in vitro. The iHep cells had multiple hepatocyte-specific features and reconstituted damaged hepatic tissues after transplantation.


REFERENCES

  1. Avraham, K. B., Prezioso, V. R., Chen, W. S., Lai, E., Sladek, F. M., Zhong, W., Darnell, J. E., Jr., Jenkins, N. A., Copeland, N. G. Murine chromosomal location of four hepatocyte-enriched transcription factors: HNF-3-alpha, HNF-3-beta, HNF-3-gamma, and HNF-4. Genomics 13: 264-268, 1992. [PubMed: 1612587, related citations] [Full Text]

  2. Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., Hui, L. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475: 386-389, 2011. [PubMed: 21562492, related citations] [Full Text]

  3. Kaestner, K. H., Hiemisch, H., Luckow, B., Schutz, G. The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence, and mRNA distribution. Genomics 20: 377-385, 1994. [PubMed: 8034310, related citations] [Full Text]

  4. Mincheva, A., Lichter, P., Schutz, G., Kaestner, K. H. Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, 20p11, and 19q13.2-q13.4. Genomics 39: 417-419, 1997. [PubMed: 9119385, related citations] [Full Text]

  5. Sekiya, S., Suzuki, A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475: 390-393, 2011. [PubMed: 21716291, related citations] [Full Text]


Contributors:
Ada Hamosh - updated : 8/4/2011
Creation Date:
Jennifer P. Macke : 1/29/1998
carol : 04/15/2014
carol : 4/15/2014
alopez : 8/15/2011
terry : 8/4/2011
tkritzer : 12/10/2002
carol : 9/18/2002
carol : 2/13/1998
carol : 2/4/1998

* 602295

FORKHEAD BOX A3; FOXA3


Alternative titles; symbols

HEPATOCYTE NUCLEAR FACTOR 3-GAMMA; HNF3G


HGNC Approved Gene Symbol: FOXA3

Cytogenetic location: 19q13.32     Genomic coordinates (GRCh38): 19:45,864,326-45,873,797 (from NCBI)


TEXT

Description

The hepatocyte nuclear factors (see HNF1A, 142410) are transcriptional activators for liver-specific transcripts such as albumin and transthyretin. The HNF3 family, including HNF3A (602294), HNF3B (600288), and HNF3G, are members of the forkhead class of DNA-binding proteins (Kaestner et al., 1994).


Cloning and Expression

Kaestner et al. (1994) cloned the mouse Hnf3a, Hnf3b, and Hnf3g genes. The genes encode polypeptides of 468, 459, and 354 amino acids, respectively. Both Hnf3a and Hnf3b are expressed in tissues of endodermal origin, i.e., stomach, intestines, liver, and lung, whereas Hnf3g is more extensively expressed, being present additionally in ovary, testis, heart, and adipose tissue, but missing from lung.


Mapping

Mincheva et al. (1997) used fluorescence in situ hybridization to map the HNF3G gene to chromosome 19q13.2-q13.4. By analysis of RFLPs in interspecific backcross mice, Avraham et al. (1992) mapped the mouse Hnf3-gamma gene to the proximal region of chromosome 7.


Gene Function

Huang et al. (2011) demonstrated the direct induction of functional hepatocyte-like (induced hepatocyte, iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4 (600576), Hnf1-alpha (142410), and Foxa3 and inactivation of p19(Arf) (600160). iHep cells showed typical epithelial morphology, expressed hepatic genes, and acquired hepatocyte functions. Notably, transplanted iHep cells repopulated the livers of fumarylacetoacetate hydrolase-deficient (Fah-null; see 613871) mice and rescued almost half of recipients from death by restoring liver functions.

Sekiya and Suzuki (2011) screened the effects of 12 candidate factors to identify 3 specific combinations of 2 transcription factors, comprising Hnf4-alpha (600281) plus Foxa1 (602294), Foxa2 (600288), or Foxa3, that can convert mouse embryonic and adult fibroblasts into cells (iHep) that closely resemble hepatocytes in vitro. The iHep cells had multiple hepatocyte-specific features and reconstituted damaged hepatic tissues after transplantation.


REFERENCES

  1. Avraham, K. B., Prezioso, V. R., Chen, W. S., Lai, E., Sladek, F. M., Zhong, W., Darnell, J. E., Jr., Jenkins, N. A., Copeland, N. G. Murine chromosomal location of four hepatocyte-enriched transcription factors: HNF-3-alpha, HNF-3-beta, HNF-3-gamma, and HNF-4. Genomics 13: 264-268, 1992. [PubMed: 1612587] [Full Text: https://doi.org/10.1016/0888-7543(92)90241-j]

  2. Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., Hui, L. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475: 386-389, 2011. [PubMed: 21562492] [Full Text: https://doi.org/10.1038/nature10116]

  3. Kaestner, K. H., Hiemisch, H., Luckow, B., Schutz, G. The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence, and mRNA distribution. Genomics 20: 377-385, 1994. [PubMed: 8034310] [Full Text: https://doi.org/10.1006/geno.1994.1191]

  4. Mincheva, A., Lichter, P., Schutz, G., Kaestner, K. H. Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, 20p11, and 19q13.2-q13.4. Genomics 39: 417-419, 1997. [PubMed: 9119385] [Full Text: https://doi.org/10.1006/geno.1996.4477]

  5. Sekiya, S., Suzuki, A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475: 390-393, 2011. [PubMed: 21716291] [Full Text: https://doi.org/10.1038/nature10263]


Contributors:
Ada Hamosh - updated : 8/4/2011

Creation Date:
Jennifer P. Macke : 1/29/1998

Edit History:
carol : 04/15/2014
carol : 4/15/2014
alopez : 8/15/2011
terry : 8/4/2011
tkritzer : 12/10/2002
carol : 9/18/2002
carol : 2/13/1998
carol : 2/4/1998