The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation

Sham, Mai Har; Vesque, Christine; Nonchev, Stefan; Marshall, Heather; Frain, Monique; Gupta, Romita Das; Whiting, Jenny; Wilkinson, David; Charnay, Patrick; Krumlauf, Robb

doi:10.1016/0092-8674(93)90659-e

Cited by 290 publications

(201 citation statements)

References 58 publications

Supporting

Mentioning

195

Contrasting

Unclassified

Order By: Relevance

“…We found six possible EGR2-binding sequences (Chavrier et al, 1990;Nardelli et al, 1991;Sham et al, 1993) in the promoter region (À1 to À349) of the BNIP3L gene and two in the promoter region (À18 to À338) of the BAK gene. Figure 5a illustrates the construction of reporter plasmids in which various lengths of the promoter regions of BNIP3L (P1-P6) and BAK (P1-P3) were subcloned into pGL3-basic vector.…”

Section: Direct Regulation Of Bnip3l and Bak Expression By Egr2mentioning

confidence: 99%

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Unoki

Nakamura

2003

Oncogene

View full text Add to dashboard Cite

EGR2 plays a key role in the PTEN-induced apoptotic pathway. Using adenovirus-mediated gene transfer to 39 cancer cell lines, we found that EGR2 could induce apoptosis in a large proportion of these lines by altering the permeability of mitochondrial membranes, releasing cytochrome c and activating caspase-3, -8, and -9. Analysis by cDNA microarray and subsequent functional studies revealed that EGR2 directly transactivates expression of BNIP3L and BAK. Our results helped to clarify the molecular mechanism of the apoptotic pathway induced by PTEN-EGR2, and suggested that EGR2 may be an excellent target molecule for gene therapy to treat a variety of cancers.

show abstract

Section: Direct Regulation Of Bnip3l and Bak Expression By Egr2mentioning

confidence: 99%

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Unoki

Nakamura

2003

Oncogene

View full text Add to dashboard Cite

show abstract

“…Treatment of embryos with exogenous RA, or conditions that disrupt RA signaling, result in changes in Hox gene expression and fundamental changes in hindbrain patterning (Papalopulu et al, 1991;Marshall et al, 1992;Simeone et al, 1995;Alexandre et al, 1996;Maden et al, 1996;Dupe et al, 1999;Niederreither et al, 2000;White et al, 2000). Several other segmentation genes, Krox20,vhnf1,and Kreisler/valentino (mafB), regulate even earlier stages of hindbrain segmentation and are required for normal activation of various Hox genes (Sham et al, 1993;Nonchev et al, 1996;Manzanares et al, 1997Manzanares et al, , 1999Prince et al, 1998). Krox20 is expressed in rhombomeres 3 and 5 (r3 and r5), which fail to form in krox20 mutant mice (Swiatek and Gridley, 1993).…”

Section: Introductionmentioning

confidence: 99%

Rhombomere boundaries are Wnt signaling centers that regulate metameric patterning in the zebrafish hindbrain

Riley

Chiang

Storch

et al. 2004

Developmental Dynamics

View full text Add to dashboard Cite

The vertebrate hindbrain develops from a series of segments (rhombomeres) distributed along the anteroposterior axis. We are studying the roles of Wnt and Delta-Notch signaling in maintaining rhombomere boundaries as organizing centers in the zebrafish hindbrain. Several wnt genes (wnt1, wnt3a, wnt8b, and wnt10b) show elevated expression at rhombomere boundaries, whereas several delta genes (dlA, dlB, and dlD) are expressed in transverse stripes flanking rhombomere boundaries. Partial disruption of Wnt signaling by knockdown of multiple wnt genes, or the Wnt mediator tcf3b, ablates boundaries and associated cell types. Expression of dlA is chaotic, and cell types associated with rhombomere centers are disorganized. Similar patterning defects are observed in segmentation mutants spiel-ohne-grenzen (spg) and valentino (val), which fail to form rhombomere boundaries due to faulty interactions between adjacent rhombomeres. Stripes of wnt expression are variably disrupted, with corresponding disturbances in metameric patterning. Mutations in dlA or mind bomb (mib) disrupt Delta-Notch signaling and cause a wide range of patterning defects in the hindbrain. Stripes of wnt1 are initially normal but subsequently dissipate, and metameric patterning becomes increasingly disorganized. Driving wnt1 expression using a heat-shock construct partially rescues metameric patterning in mib mutants. Thus, rhombomere boundaries act as Wnt signaling centers required for precise metameric patterning, and Delta signals from flanking cells provide feedback to maintain wnt expression at boundaries. Similar feedback mechanisms operate in the Drosophila wing disc and vertebrate limb bud, suggesting coaptation of a conserved signaling module that spatially organizes cells in complex organ systems.

show abstract

“…Transient transfection experiments demonstrated that NGFI-A, Krox20 (33), NGFI-C (11), and Egr3 (47) could all activate transcription from this sequence, whereas WT1 was found to repress transcription from this site (16,52). Identical or highly similar sites have been shown to be functional regulatory elements in the promoters of acetylcholinesterase (35), desmin (36), adenosine deaminase (1), insulin-like growth factor II (16), and HoxB2 (56). The single GCGGGGGCG binding site has frequently been referred to as the consensus binding site for the NGFI-A family of transcription factors on the basis of its presence in a limited number of natural gene promoters.…”

mentioning

confidence: 99%

DNA-Binding Specificity of NGFI-A and Related Zinc Finger Transcription Factors

Swirnoff

Milbrandt

1995

Molecular and Cellular Biology

299

287

View full text Add to dashboard Cite

NGFI-A is the prototypic member of a family of immediate-early gene-encoded transcription factors which includes NGFI-C, Egr3, and Krox20. These proteins possess highly homologous DNA-binding domains, composed of three Cys 2 -His 2 zinc fingers, and all bind to and activate transcription from the sequence GCGGGGGCG. We used a PCR-mediated random site selection protocol to determine whether other sites could be bound by these proteins and the extent to which their binding site preferences are similar or different. The high-affinity consensus sites generated from the selection data are similar, and the combined consensus sequence is T -G-C-G-T/g-G/A-G-G-C/a/t-G-G/T (lowercase letters indicate bases selected less frequently).Using gel shift assays, we found that sequences that diverge from the consensus were bound by NGFI-A, confirming that there is greater variability in binding sites than has generally been acknowledged. We also provide evidence that protein-DNA interactions not noted, or whose importance was not apparent from the X-ray cocrystal structure of the NGFI-A zinc fingers complexed with DNA, contribute significantly to the binding energy of these proteins and confirm that an optimal site is at least 10 instead of 9 nucleotides in length. In contrast to the similarities in binding specificity among these proteins, we found that while NGFI-A, Egr3, and Krox20 have comparable DNA binding affinities and kinetics of dissociation, the affinity of NGFI-C is more than threefold lower. This could result in differential regulation of target genes in cells where NGFI-C and the other proteins are coexpressed. Furthermore, we show that this affinity difference is a property not of the zinc fingers themselves but rather of the protein context of the DNA-binding domain.

show abstract

The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation

Cited by 290 publications

References 58 publications

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Rhombomere boundaries are Wnt signaling centers that regulate metameric patterning in the zebrafish hindbrain

DNA-Binding Specificity of NGFI-A and Related Zinc Finger Transcription Factors

Contact Info

Product

Resources

About