A reciprocal translocation dissects roles of <i>Pax6</i> alternative promoters and upstream regulatory elements in the development of pancreas, brain, and eye

Elso, Colleen M.; Lü, Xing; Weisner, Patricia A.; Thompson, Heather L.; Skinner, Andrea; Carver, Ethan A.; Stubbs, Lisa

doi:10.1002/dvg.22409

Cited by 19 publications

(19 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PAX6 is a member of the PAX gene family and acts as a key regulator in the development of the eyes, central nervous system and pancreas (15,32,33). Furthermore, it has been demonstrated that PAX6 serves an oncogenic role in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Paired box (PAX) 6, a member of the PAX family, is an important transcription factor associated with the development of the eyes, pancreas and central nervous system (14,15). Furthermore, it has been established that deregulated PAX6 is involved different types of human cancer, including non-small cell lung cancer (16), retinoblastoma (17), glioma (18), colorectal cancer (19), prostate cancer (20) and breast cancer (21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

Zou

Huang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. MicroRNAs (miRs) are a type of small non-coding RNA that serve crucial roles in the development and progression of breast cancer. However, the exact role and underlying molecular mechanism of miR-375 in mediating the growth and metastasis of breast cancer remains unknown. In the present study, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to examine RNA and protein expression. A luciferase reporter assay was performed to determine the association between miR-375 and paired box 6 (PAX6). The results of the current study indicate that the expression of miR-375 was reduced in breast cancer tissues compared with matched adjacent normal tissues. Transfection with miR-375 mimics led to a significant increase in levels of miR-375 in human breast cancer Michigan Cancer Foundation (MCF)-7 cells (P<0.05). The increase in miR-375 expression caused a significant decrease in the viability, migration and invasion of MCF-7 cells (P<0.05), accompanied by a reduced expression of matrix metalloproteinase (MMP) 2 and MMP9 proteins. Luciferase reporter assay identified PAX6 as a novel target of miR-375 and miR-375 in turn, negatively regulated the protein expression of PAX6 in MCF-7 cells. By contrast, overexpression of PAX6 led to a significant increase in MCF-7 cell viability (P<0.01) but did not affect the migration and invasion of MCF-7 cells, suggesting that the inhibitory effect of miR-375 on MCF-7 cell viability may be occurring, in part, via the direct targeting of PAX6.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

Zou

Huang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The results indicated that the mutation occurred as a clean breakage-and-reunion event (Fig. 3A) very similar to those documented in the analysis of other germline translocations (Elso et al, 2008; 2013; Elso, 2004). …”

Section: Resultssupporting

confidence: 81%

A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues

Bolt

Elso

Lü

et al. 2014

Developmental Biology

Self Cite

View full text Add to dashboard Cite

The vertebrate T-box transcription factor gene Tbx18 performs a vital role in development of multiple organ systems. Tbx18 insufficiency manifests as recessive phenotypes in the upper urinary system, cardiac venous pole, inner ear, and axial skeleton; homozygous null mutant animals die perinatally. Here, we report a new regulatory mutation of Tbx18, a reciprocal translocation breaking 78 kbp downstream of the gene. 12Gso homozygotes present urinary and vertebral defects very similar to those associated with Tbx18-null mutations, but 12Gso is clearly not a global null allele since homozygotes survive into adulthood. We show that 12Gso down-regulates Tbx18 expression in a manner that is both spatially- and temporally-specific; combined with other data, the mutation points particularly to the presence of an essential urogenital enhancer located near the translocation breakpoint site. In support of this hypothesis, we identify a distal enhancer element, ECR1, which is active in developing urogenital and other tissues; we propose that disruption of this element leads to premature loss of Tbx18 function in 12Gso mutant mice. These data reveal a long-range regulatory architecture extending far downstream ofTbx18, identify a novel and likely essential urogenital enhancer, and introduce a new tool for dissecting postnatal phenotypes associated with dysregulation of Tbx18.

show abstract

“…Slides were baked at 41 ° C overnight and stored at −20 ° C until use. Slides were pretreated and hybridizations were performed as described previously [58]. Sections were mounted using Vectashield Mounting Medium with DAPI.…”

Section: Methodsmentioning

confidence: 99%

ZSCAN5B and primate-specific paralogs bind RNA polymerase III genes and extra-TFIIIC (ETC) sites to modulate mitotic progression

et al. 2016

Self Cite

View full text Add to dashboard Cite

Mammalian genomes contain hundreds of genes transcribed by RNA Polymerase III (Pol III), encoding noncoding RNAs and especially the tRNAs specialized to carry specific amino acids to the ribosome for protein synthesis. In addition to this well-known function, tRNAs and their genes (tDNAs) serve a variety of other critical cellular functions. For example, tRNAs and other Pol III transcripts can be cleaved to yield small RNAs with potent regulatory activities. Furthermore, from yeast to mammals, active tDNAs and related “extra-TFIIIC” (ETC) loci provide the DNA scaffolds for the most ancient known mechanism of three-dimensional chromatin architecture. Here we identify the ZSCAN5 TF family - including mammalian ZSCAN5B and its primate-specific paralogs - as proteins that occupy mammalian Pol III promoters and ETC sites. We show that ZSCAN5B binds with high specificity to a conserved subset of Pol III genes in human and mouse. Furthermore, primate-specific ZSCAN5A and ZSCAN5D also bind Pol III genes, although ZSCAN5D preferentially localizes to MIR SINE- and LINE2-associated ETC sites. ZSCAN5 genes are expressed in proliferating cell populations and are cell-cycle regulated, and siRNA knockdown experiments suggested a cooperative role in regulation of mitotic progression. Consistent with this prediction, ZSCAN5A knockdown led to increasing numbers of cells in mitosis and the appearance of cells. Together, these data implicate the role of ZSCAN5 genes in regulation of Pol III genes and nearby Pol II loci, ultimately influencing cell cycle progression and differentiation in a variety of tissues.

show abstract

A reciprocal translocation dissects roles of Pax6 alternative promoters and upstream regulatory elements in the development of pancreas, brain, and eye

Cited by 19 publications

References 45 publications

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues

ZSCAN5B and primate-specific paralogs bind RNA polymerase III genes and extra-TFIIIC (ETC) sites to modulate mitotic progression

Contact Info

Product

Resources

About