p300/CBP Acts as a Coactivator of the Cone–Rod Homeobox Transcription Factor

Yanagi, Yasuo; Masuhiro, Yoshikazu; Mori, Mikiro; Yanagisawa, Junn; Kato, Shigeaki

doi:10.1006/bbrc.2000.2304

Cited by 29 publications

(33 citation statements)

References 22 publications

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“…Thus, one possible mechanism for Crx transcription activation is to promote chromatin remodeling by recruiting STAGA or other HAT-containing coactivators to its target genes. This possibility is further supported by the findings that Crx also interacts with two other coactivators with intrinsic HAT activity, Cbp and p300 [ (Yanagi et al, 2000); and data not shown].…”

Section: Mechanisms Of Actionmentioning

confidence: 53%

“…These include photoreceptor-specific transcription factors [Nrl and Nr2e3, discussed below; Qrx ] and general transcription factors [Sp family members (Lerner et al, 2001); and nuclear receptor Ror isoforms ]. Crx also interacts with chromatin remodeling factors [ataxin-7 (La Spada et al, 2001), HMG I/Y (Chau et al, 2000), Baf ], the transcription coactivators Cbp and p300 (Yanagi et al, 2000), and the STAGA coactivator/chromatin remodeling complex (Palhan et al, 2005). STAGA is a highly conserved multi-protein complex present from yeast (SAGA) to man .…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

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Regulation of photoreceptor gene expression by Crx-associated transcription factor network

2008

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Rod and cone photoreceptors in the mammalian retina are special types of neurons that are responsible for phototransduction, the first step of vision. Development and maintenance of photoreceptors require precisely regulated gene expression. This regulation is mediated by a network of photoreceptor transcription factors centered on Crx, an Otx-like homeodomain transcription factor. The cell type (subtype) specificity of this network is governed by factors that are preferentially expressed by rods or cones or both, including the rod-determining factors neural retina leucine zipper protein (Nrl) and the orphan nuclear receptor Nr2e3; and cone-determining factors, mostly nuclear receptor family members. The best-documented of these include thyroid hormone receptor β2 (Trβ2), retinoid related orphan receptor Rorβ, and retinoid X receptor Rxrγ. The appropriate function of this network also depends on general transcription factors and co-factors that are ubiquitously expressed, such as the Sp zinc finger transcription factors and STAGA coactivator complexes. These cell type-specific and general transcription regulators form complex interactomes; mutations that interfere with any of the interactions can cause photoreceptor development defects or degeneration. In this manuscript, we review recent progress on the roles of various photoreceptor transcription factors and interactions in photoreceptor subtype development. We also provide evidence of auto-, para-, and feedback regulation among these factors at the transcriptional level. These protein-protein and protein-promoter interactions provide precision and specificity in controlling photoreceptor subtype-specific gene expression, development and survival. Understanding these interactions may provide insights to more effective therapeutic interventions for photoreceptor diseases.

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Section: Mechanisms Of Actionmentioning

confidence: 53%

Section: Mechanisms Of Actionmentioning

confidence: 99%

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

2008

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“…Several studies have identified Crx-interacting proteins, such as Nrl (15), CREB-binding protein/p300 (25), phosducin and phosducin-like proteins (PhLP1 and PhLOP1) (26), the nonhistone high mobility group protein HMGA1 (formerly HMG19Y) (27), and ataxin-7 (28). Among these, Nrl, HMGA1, and CREB-binding protein/p300 enhance, whereas Phd (PhLPs) and ataxin-7 repress, the transactivation activity of Crx.…”

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confidence: 99%

Barrier to Autointegration Factor Interacts with the Cone-Rod Homeobox and Represses Its Transactivation Function

Wang

Rivolta

et al. 2002

Journal of Biological Chemistry

115

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Crx (cone-rod homeobox) is a homeodomain transcription factor implicated in regulating the expression of photoreceptor and pineal genes. To identify proteins that interact with Crx in the retina, we carried out a yeast two-hybrid screen of a retinal cDNA library. One of the identified clones encodes Baf (barrier to autointegration factor), which was previously shown to have a role in mitosis and retroviral integration. Additional biochemical assays provided supporting evidence for a Baf-Crx interaction. The Baf protein is detectable in all nuclear layers of the mouse retina, including the photoreceptors and the bipolar cells where Crx is expressed. Transient transfection assays with a rhodopsin-luciferase reporter in HEK293 cells demonstrate that overexpression of Baf represses Crx-mediated transactivation, suggesting that Baf acts as a negative regulator of Crx. Consistent with this role for Baf, an E80A mutation of CRX associated with cone-rod dystrophy has a higher than normal transactivation potency but a reduced interaction with Baf. Although our studies did not identify a causative Baf mutation in retinopathies, we suggest that Baf may contribute to the phenotype of a photoreceptor degenerative disease by modifying the activity of Crx. In view of the ubiquitous expression of Baf, we hypothesize that it may play a role in regulating tissueor cell type-specific gene expression by interacting with homeodomain transcription factors.Development and maintenance of photoreceptor function in mammalian retina requires the expression of photoreceptorspecific or photoreceptor-enriched genes. Under-or over-

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“…In vertebrates, many of these enzymes are members of gene families that show high degrees of homology and, in some cases, functional redundancy. This is true for the beststudied HATs in the retina, KAT3A/CBP and KAT3B/p300 [36,88,89], and KAT2A/GCN5 [90][91][92] and KAT2B/ PCAF. CBP and p300 acetylate both histone H3 and histone H4 (Table 3).…”

Section: Histone Acetylation In Retinal Ganglion Cellsmentioning

confidence: 72%

“…CRX protein binds CBP and p300 directly [88,89], and GCN5 indirectly via interaction with ataxin-7, a polyglutamine-containing component of the STAGA complex [90][91][92]. CRX recruitment of these HATs to photoreceptor gene promoters leads to increased H3 and H4 acetylation and transcription activation of CRX target genes.…”

Section: Histone Modifications In Photoreceptor Gene Expressionmentioning

confidence: 99%

Epigenetic regulation of retinal development and disease

Rao

Hennig

Malik

et al. 2011

j ocul biol dis inform

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Epigenetic regulation, including DNA methylation, histone modifications, and chromosomal organization, is emerging as a new layer of transcriptional regulation in retinal development and maintenance. Guided by intrinsic transcription factors and extrinsic signaling molecules, epigenetic regulation can activate and/or repress the expression of specific sets of genes, therefore playing an important role in retinal cell fate specification and terminal differentiation during development as well as maintaining cell function and survival in adults. Here, we review the major findings that have linked these mechanisms to the development and maintenance of retinal structure and function, with a focus on ganglion cells and photoreceptors. The mechanisms of epigenetic regulation are highly complex and vary among different cell types. Understanding the basic principles of these mechanisms and their regulatory pathways may provide new insight into the pathogenesis of retinal diseases associated with transcription dysregulation, and new therapeutic strategies for treatment.

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p300/CBP Acts as a Coactivator of the Cone–Rod Homeobox Transcription Factor

Cited by 29 publications

References 22 publications

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

Barrier to Autointegration Factor Interacts with the Cone-Rod Homeobox and Represses Its Transactivation Function

Epigenetic regulation of retinal development and disease

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