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Using mouse models to study function of transcriptional factors in T cell development.

Li P, Xiao Y, Liu Z, Liu P - Cell Regen (Lond) (2012)

Bottom Line: With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells.Transcriptional factors play important role in hematopoiesis.Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, Guangzchou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China.

ABSTRACT
Laboratory mice have widely been used as tools for basic biological research and models for studying human diseases. With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells. Transcriptional factors play important role in hematopoiesis. In this review we compile several studies on using genetic modified mice and humanized mice to study function of transcriptional factors in lymphopoiesis, including T lymphocyte and Natural killer (NK) cell development. Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

No MeSH data available.


Related in: MedlinePlus

Structure of human Bcl11b protein.A: The bar represents the 3 isoforms of Bcl11a. Exons 1-3 are the same in all the 3 isoforms. Isoform 1 is the longest one containing 835 amino acids. The 4th exon contains all the 6 Zinc-fingers domains. The longest isoform comprised exons 1-4, whereas the 2 common shorter isoforms exhibited alternative splicing from within exon 4 to an additional exon 5. B: The bar represents the isoform 1 of Bcl11b including 4 exons and 6 Zinc-finger domains. All the 6 Zinc-finger domains are distributed within the longest exon 4, and the exons 1–3 are in length of 214 amino acids. The 2nd and 3rd Zinc-finger domains are responsible for DNA binding. The regions shown by lines encodes domains that bind to various Bcl11b cooperating proteins, such as HDAC1/2 (histone deacetylase), SIRT2 (sirtuin family protein), SUV39H1 (histone methyltransferase), MTA1/2 (metastasis-associated proteins), RbAp46/48 (Rb-associated protein).
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Fig4: Structure of human Bcl11b protein.A: The bar represents the 3 isoforms of Bcl11a. Exons 1-3 are the same in all the 3 isoforms. Isoform 1 is the longest one containing 835 amino acids. The 4th exon contains all the 6 Zinc-fingers domains. The longest isoform comprised exons 1-4, whereas the 2 common shorter isoforms exhibited alternative splicing from within exon 4 to an additional exon 5. B: The bar represents the isoform 1 of Bcl11b including 4 exons and 6 Zinc-finger domains. All the 6 Zinc-finger domains are distributed within the longest exon 4, and the exons 1–3 are in length of 214 amino acids. The 2nd and 3rd Zinc-finger domains are responsible for DNA binding. The regions shown by lines encodes domains that bind to various Bcl11b cooperating proteins, such as HDAC1/2 (histone deacetylase), SIRT2 (sirtuin family protein), SUV39H1 (histone methyltransferase), MTA1/2 (metastasis-associated proteins), RbAp46/48 (Rb-associated protein).

Mentions: The B-cell lymphoma/leukemia 11 (Bcl11) family has two members, Bcl11a and Bcl11b. Both of them are Kruppel-like C2H2 type zinc finger transcription factors [103]. Bcl11a was first discovered as a retroviral insertion site (Evi9) in myeloid leukemia tumors in the BXH-2 mouse [104]. Located at 2p16.1, Bcl11a is consists of 5 exons and encodes three different isoforms (Figure 4A). The first three exons of Bcl11a present in all the three isoforms. The longest isoform comprised exon 1-4, whereas the rest two common shorter isoforms exhibited alternative splicing from within exon 4 to an additional exon 5. However, the exon 5 in the isoform 2 is different from the one in the isoform 3 due to frame shift in their exon 4.Figure 4


Using mouse models to study function of transcriptional factors in T cell development.

Li P, Xiao Y, Liu Z, Liu P - Cell Regen (Lond) (2012)

Structure of human Bcl11b protein.A: The bar represents the 3 isoforms of Bcl11a. Exons 1-3 are the same in all the 3 isoforms. Isoform 1 is the longest one containing 835 amino acids. The 4th exon contains all the 6 Zinc-fingers domains. The longest isoform comprised exons 1-4, whereas the 2 common shorter isoforms exhibited alternative splicing from within exon 4 to an additional exon 5. B: The bar represents the isoform 1 of Bcl11b including 4 exons and 6 Zinc-finger domains. All the 6 Zinc-finger domains are distributed within the longest exon 4, and the exons 1–3 are in length of 214 amino acids. The 2nd and 3rd Zinc-finger domains are responsible for DNA binding. The regions shown by lines encodes domains that bind to various Bcl11b cooperating proteins, such as HDAC1/2 (histone deacetylase), SIRT2 (sirtuin family protein), SUV39H1 (histone methyltransferase), MTA1/2 (metastasis-associated proteins), RbAp46/48 (Rb-associated protein).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230505&req=5

Fig4: Structure of human Bcl11b protein.A: The bar represents the 3 isoforms of Bcl11a. Exons 1-3 are the same in all the 3 isoforms. Isoform 1 is the longest one containing 835 amino acids. The 4th exon contains all the 6 Zinc-fingers domains. The longest isoform comprised exons 1-4, whereas the 2 common shorter isoforms exhibited alternative splicing from within exon 4 to an additional exon 5. B: The bar represents the isoform 1 of Bcl11b including 4 exons and 6 Zinc-finger domains. All the 6 Zinc-finger domains are distributed within the longest exon 4, and the exons 1–3 are in length of 214 amino acids. The 2nd and 3rd Zinc-finger domains are responsible for DNA binding. The regions shown by lines encodes domains that bind to various Bcl11b cooperating proteins, such as HDAC1/2 (histone deacetylase), SIRT2 (sirtuin family protein), SUV39H1 (histone methyltransferase), MTA1/2 (metastasis-associated proteins), RbAp46/48 (Rb-associated protein).
Mentions: The B-cell lymphoma/leukemia 11 (Bcl11) family has two members, Bcl11a and Bcl11b. Both of them are Kruppel-like C2H2 type zinc finger transcription factors [103]. Bcl11a was first discovered as a retroviral insertion site (Evi9) in myeloid leukemia tumors in the BXH-2 mouse [104]. Located at 2p16.1, Bcl11a is consists of 5 exons and encodes three different isoforms (Figure 4A). The first three exons of Bcl11a present in all the three isoforms. The longest isoform comprised exon 1-4, whereas the rest two common shorter isoforms exhibited alternative splicing from within exon 4 to an additional exon 5. However, the exon 5 in the isoform 2 is different from the one in the isoform 3 due to frame shift in their exon 4.Figure 4

Bottom Line: With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells.Transcriptional factors play important role in hematopoiesis.Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, Guangzchou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China.

ABSTRACT
Laboratory mice have widely been used as tools for basic biological research and models for studying human diseases. With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells. Transcriptional factors play important role in hematopoiesis. In this review we compile several studies on using genetic modified mice and humanized mice to study function of transcriptional factors in lymphopoiesis, including T lymphocyte and Natural killer (NK) cell development. Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

No MeSH data available.


Related in: MedlinePlus