Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family

Eberhard, Dirk; Jiménez, Gerardo; Heavey, Barry; Busslinger, Meinrad

doi:10.1093/emboj/19.10.2292

Cited by 233 publications

(213 citation statements)

References 48 publications

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“…Members of the other subgroup, e.g., Grg5 in mice and AES in humans, contain the amino-terminal region of gro, including the Q-rich domain, but lack most of the variable region and the entire WD-40 repeat region. Mammalian gro homologues in the first group bind to transcription factors that target gene repression (Aronson et al, 1997;Roose et al, 1998;Eberhard et al, 2000;Tetsuka et al, 2000;Wang et al, 2000;Brantjes et al, 2001), whereas the short form of gro, such as XGrg5 in Xenopus, has been shown to enhance transcriptional activity (Roose et al, 1998;Brantjes et al, 2001). It has been speculated that Grg5 may act as a dominant negative molecule within a transcription complex.…”

Section: Introductionmentioning

confidence: 99%

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Wang

Plotkina

et al. 2002

Developmental Dynamics

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Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4 -5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates.

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Section: Introductionmentioning

confidence: 99%

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Wang

Plotkina

et al. 2002

Developmental Dynamics

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“…All members of the Bar-homeodomain family have one or more N-terminal engrailed homology-1 (eh-1) motifs, which are generally recognized as recruitment points for TLE͞Groucho-related factors. Mammalian homologs of Drosophila Groucho have been repeatedly identified as important corepressors for homeodomain proteins and other transcription factors (13)(14)(15)(16)(17)(18). In the skin, TLE͞Groucho factors acting through Tcf3 have been implicated in suppressing the terminal differentiation of epidermis (19).…”

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confidence: 99%

Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling

Olson

Zhang

Taylor

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The hair-growth cycle, a complex biological system requiring coordinate alterations in gene expression and cellular behavior, provides a challenging model for investigating the interplay of specific transcriptional regulation events. Here we report that the Barx2 homeodomain factor serves as a regulator of hair follicle remodeling (catagen), and loss of Barx2 in mice causes a defect both in the initiation and progression of catagen, resulting in a protracted first catagen, and later, causing short hair in adult gene-deleted mice. Barx2 negatively regulates its own promoter, and our study highlights the role of Barx2 as a repressor in the skin that can, unexpectedly, functionally interact with two WD40-domain factors distantly related to the yeast corepressor Tup1. These two corepressors, transducin-like enhancer of split and transducin ␤-like 1, function through distinct and independent interactions with Barx2 for the repression of gene targets, including the Barx2 gene itself, emphasizing the roles of complementary repression strategies in engrailed homology-1 motif-containing homeodomain factors. Together, our data suggest that the hairremodeling defect of Barx2 mutant mice could be explained, in part, by failure to repress one or more critical target genes.A distinctive feature of the hair follicle is its periodic regeneration and degeneration throughout the lifetime of the organism in cycles of three phases: anagen, catagen, and telogen. In mice, hair follicle morphogenesis begins late in development and continues through growth, or anagen, of the first pelage until Ϸ2 weeks after birth. The final length of the hair is genetically determined by the period spent in anagen, with hair-generating cells of the bulb having a finite proliferative capacity that is influence by factors from the dermal papilla and surrounding tissues. Anagen terminates with the destruction of the growing part of the follicle in a remodeling process called catagen. Thereafter, a resting period, or telogen, intervenes with the finished hair normally retained in the diminutive follicle, until anagen reinitiates with the start of a new cycle of hair growth (1, 2). Two synchronous cycles of hair growth occur in juvenile mice, with consecutive waves of anagen-catagen-telogen moving from neck to tail, and thereafter only smaller patches of follicles cycle together in adult mice. From the human perspective, hair follicle remodeling is important because changes in the hair cycle underlie most disorders involving unwanted hair growth or loss (3, 4). Evidence is also emerging that hair cycling and wound healing share some basic molecular strategies (5).The transcriptional control of skin and hair development, and regulation of postnatal, cycling hair follicles, represents a complex system involving the coordinated actions of many intracellular signaling molecules and transcription factors. Recently, expression profiling has been used to systematically identify hair-cycle-associated genes and cluster them into major classes of expression over the...

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“…But until now, the precise molecular mechanisms of Pax2 in the mullerian duct development remain obscure. Early studies showed that the Pax2 protein could interact with some repressor proteins to change the positive regulators to negative during the period of transcription [28]. In recent works, scholars identified that the Pax2 transactivation domain is phosphorylated by the c-Jun N-terminal kinase (JNK) [29].…”

Section: Discussionmentioning

confidence: 99%

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females

Xing

et al. 2016

J Assist Reprod Genet

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Purpose The study aims to investigate the genetic association between paired box gene 2 (PAX2) and mullerian duct anomalies (MDA) in Chinese Han females. Methods Matrix-assisted laser desorption/ionization time-offlight mass spectrometry (MALDI-TOF MS) was used to identify the genotypes of three tag single nucleotide polymorphisms (SNPs) in PAX2 in 362 MDA cases and 406 controls. Results We found that one tag SNP (rs12266644) of PAX2 was associated with susceptibility to MDA. The genotype distributions of the SNP rs12266644 have a statistically significant difference in the MDA patients and controls with a p value = 0.008. In the dominant model, we also observed that the GT + TT genotype increased the risk for MDA (p = 0.015, OR = 1.637, 95 % CI = 1.096-2.443). Conclusion The polymorphism rs12266644 of PAX2 might be a risk factor for MDA in Chinese Han females.

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Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family

Cited by 233 publications

References 48 publications

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females

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