Transcriptional Activity of the Paired-like Homeodomain Proteins CHX10 and VSX1

Dorval, Kimberley M.; Bobechko, Brian P.; Ahmad, Kami; Bremner, Rod

doi:10.1074/jbc.m412676200

Cited by 49 publications

(57 citation statements)

References 79 publications

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“…In the HD of Prrxl1, this residue is a glutamine (Gln 50 ), suggesting that Prrxl1 binds to bipartite sequence TAAT-(N) 3 ATTA, as described for paired-like homeoprotein Chx10 [10]. Consistent with this, two of such bipartite sites are found in a Prrxl1 response element within a 363 bp fragment of the RGMb/Dragon proximal promoter [26].…”

Section: Discussionmentioning

confidence: 64%

Paired related homeobox protein‐like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism

et al. 2014

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Edited by Ivan SadowskiKeywords: Paired related homeobox protein-like 1 Autorepression Dorsal root ganglia Dorsal spinal cord Chromatin immunoprecipitation a b s t r a c tThe homeodomain factor paired related homeobox protein-like 1 (Prrxl1) is crucial for proper assembly of dorsal root ganglia (DRG)-dorsal spinal cord (SC) pain-sensing circuit. By performing chromatin immunoprecipitation with either embryonic DRG or dorsal SC, we identified two evolutionarily conserved regions (i.e. proximal promoter and intron 4) of Prrxl1 locus that show tissuespecific binding of Prrxl1. Transcriptional assays confirm the identified regions can mediate repression by Prrxl1, while gain-of-function studies in Prrxl1 expressing ND7/23 cells indicate Prrxl1 can down-regulate its own expression. Altogether, our results suggest that Prrxl1 uses distinct regulatory regions to repress its own expression in DRG and dorsal SC.

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Section: Discussionmentioning

confidence: 64%

Paired related homeobox protein‐like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism

et al. 2014

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“…We showed that Chx10 represses transcription in vitro in several contexts (25); thus, Chx10 might inhibit photoreceptor specification at least in part through negative gene regulation. We asked whether converting Chx10 to an activator by fusing it to the VP16 activation domain would interfere with bipolar cell differentiation.…”

Section: Chx10 Drives Bipolar Cell Differentiation At the Expense Of mentioning

confidence: 88%

“…The observation that Chx10 inhibits rods, rather than other cell types, generates new models as to how this protein might act. Chx10 can repress transcription (25); thus, it may inhibit the expression of genes required for rod specification. Fusing an activation domain to Chx10 perturbs its ability to support bipolar cell differentiation, implying that repression may be a component of Chx10 function in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina

Livne-Bar

Pacal

Cheung

et al. 2006

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

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In the Chx10-null ocular retardation (or J ) mouse, retinal progenitor cell (RPC) proliferation is impaired, and bipolar neurons, a late born cell type, fail to differentiate. It is unclear whether Chx10 is required to maintain proliferation throughout retinogenesis or whether the bipolar cell defect is an indirect effect of growth arrest. We show that Chx10 is dispensable for late-stage RPC proliferation but is essential to promote bipolar cell genesis in place of rods. Ectopic Chx10 expression drove bipolar instead of rod cell differentiation without affecting division. Converting Chx10 to an activator impaired bipolar cell differentiation, implying that repression is important for Chx10 activity. In the Chx10 null or J retina, only a small fraction of cells expressing mutated Chx10 mRNA were rods, but this fraction increased after p27 Kip1 inactivation, which partially rescues proliferation. Most significantly, acute Chx10 knockdown in the postnatal retina promoted rods in place of bipolar neurons without affecting division. Thus, Chx10 directly controls bipolar cell genesis by inhibiting rod differentiation independent of its temporally limited early effect on RPC proliferation.CVC domain ͉ homeobox ͉ homeodomain ͉ short-hairpin RNA

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“…Here we have identified conserved binding sites for TF Vsx2 in the H6_10137 region, and showed that they are required to direct its regulatory activity to the neural retina domain. Vsx2 has been characterized both as a repressor and a context-specific activator 20,55,56 . In agreement with its role as a transcriptional activator, our results show that Vsx2 acts as a positive regulator of opo expression in vivo.…”

Section: Discussionmentioning

confidence: 99%

Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis

et al. 2015

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The self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain-and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.

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Transcriptional Activity of the Paired-like Homeodomain Proteins CHX10 and VSX1

Cited by 49 publications

References 79 publications

Paired related homeobox protein‐like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism

Paired related homeobox protein‐like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism

Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina

Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis

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