Promoter context determines the role of proteasome in ligand-dependent occupancy of retinoic acid responsive elements

Higazi, Aliaa M.; Abed, Mahmoud S.; Chen, Jihong; Li, Qiao

doi:10.4161/epi.6.2.13658

Cited by 15 publications

(13 citation statements)

References 55 publications

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“…4). Apart from activating gene transcription upon ligand induction, the function of RXR in the absence of ligand is also important for establishing chromatin signatures at genomic loci (40,45,46). Thus, our data suggest that RXR knockdown per se would perturb RXR-mediated chromatin modifications at regulatory loci and subsequently affect gene expression, i.e.…”

Section: Discussionmentioning

confidence: 85%

Retinoid X Receptor-selective Signaling in the Regulation of Akt/Protein Kinase B Isoform-specific Expression

AlSudais

Aabed

Nicola

et al. 2016

Journal of Biological Chemistry

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The differentiation and fusion of myoblasts into mature myotubes are complex processes responding to multiple signaling pathways. The function of Akt/PKB is critical for myogenesis, but less is clear as to the regulation of its isoform-specific expression. Bexarotene is a drug already used clinically to treat cancer, and it has the ability to enhance the commitment of embryonic stem cells into skeletal muscle lineage. Whereas bexarotene regulates fundamental biological processes through retinoid X receptor (RXR)-mediated gene expression, molecular pathways underlying its positive effects on myogenesis remain unclear. In this study, we have examined the signaling pathways that transmit bexarotene action in the context of myoblast differentiation. We show that bexarotene promotes myoblast differentiation and fusion through the activation of RXR and the regulation of Akt/PKB isoform-specific expression. Interestingly, bexarotene signaling appears to correlate with residuespecific histone acetylation and is able to counteract the detrimental effects of cachectic factors on myogenic differentiation. We also signify an isoform-specific role for Akt/PKB in RXRselective signaling to promote and to retain myoblast differentiation. Taken together, our findings establish the viability of applying bexarotene in the prevention and treatment of musclewasting disorders, particularly given the lack of drugs that promote myogenic differentiation available for potential clinical applications. Furthermore, the model of bexarotene-enhanced myogenic differentiation will provide an important avenue to identify additional genetic targets and specific molecular interactions that we can study and apply for the development of potential therapeutics in muscle regeneration and repair.

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Section: Discussionmentioning

confidence: 85%

Retinoid X Receptor-selective Signaling in the Regulation of Akt/Protein Kinase B Isoform-specific Expression

AlSudais

Aabed

Nicola

et al. 2016

Journal of Biological Chemistry

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“…At indicated time points, cells were fixed, crosslinked, and sonicated as previously described29. Chromatin DNA was purified using the Omega Bio-tek Cycle Pure Kit (Omega) and quantified using the NanoDrop Spectrophotometer (ND-1000) to ensure equal amounts of chromatin were used in the immunoprecipitation of different samples.…”

Section: Methodsmentioning

confidence: 99%

Stepwise acetyltransferase association and histone acetylation at the Myod1 locus during myogenic differentiation

Hamed

Khilji

Chen

et al. 2013

Sci Rep

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While chromatin modifications can offer a useful readout for enhancer activities, it is less clear whether these modification marks are a cause or consequence of transcription factor occupancy and enhancer activation. We have examined in details the temporal events of acetyltransferase associations and histone acetylations at different regulatory regions of the Myod1 locus. Our studies demonstrate that the histone acetyltransferase (HAT) p300 is stepwise enriched at distinct Myod1 regulatory regions during myogenic differentiation. This enrichment of p300 is associated with increased histone acetylation in a discrete pattern. Inhibition of p300 HAT activity impedes myogenic differentiation, which is coupled with decreased histone acetylation at specific Myod1 regulatory regions. We show for the first time that p300 is directly involved in the early regulation of Myod1 enhancer, and provide molecular insights into how p300 HAT activity and histone acetylation are related to enhancer activation and, consequently, gene transcription.

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“…ChIP experiments exploring the interaction of proteasome subunits with chromatin have produced contradictory results in terms of how 19S versus 20S subunits behave. Some studies have reported identical or overlapping patterns of binding for 19S and 20S proteins [ 21 , 23 , 26 , 33 , 34 , 35 ], others have focused specifically on 19S components [ 25 , 36 , 37 , 38 , 39 , 40 , 41 ], and others still have reported that 19S and 20S proteasome subunits behave differently in terms of chromatin association patterns, with significant disparity in ChIP signals of 19S versus 20S proteins [ 24 , 42 ]. At the activated GAL1 gene, for example, Gillette et al [ 42 ] reported that 19S proteins associate with the GAL1 promoter (5') soon after induction, absent of any 20S proteins, whereas 20S proteins associate later in the induction process and accumulate at the 3' end of the gene.…”

Section: The Form Of the Proteasome That Associates With Chromatinmentioning

confidence: 99%

Functions of the Proteasome on Chromatin

McCann

Tansey

2014

Biomolecules

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The proteasome is a large self-compartmentalized protease complex that recognizes, unfolds, and destroys ubiquitylated substrates. Proteasome activities are required for a host of cellular functions, and it has become clear in recent years that one set of critical actions of the proteasome occur on chromatin. In this review, we discuss some of the ways in which proteasomes directly regulate the structure and function of chromatin and chromatin regulatory proteins, and how this influences gene transcription. We discuss lingering controversies in the field, the relative importance of proteolytic versus non-proteolytic proteasome activities in this process, and highlight areas that require further investigation. Our intention is to show that proteasomes are involved in major steps controlling the expression of the genetic information, that proteasomes use both proteolytic mechanisms and ATP-dependent protein remodeling to accomplish this task, and that much is yet to be learned about the full spectrum of ways that proteasomes influence the genome.

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Promoter context determines the role of proteasome in ligand-dependent occupancy of retinoic acid responsive elements

Cited by 15 publications

References 55 publications

Retinoid X Receptor-selective Signaling in the Regulation of Akt/Protein Kinase B Isoform-specific Expression

Retinoid X Receptor-selective Signaling in the Regulation of Akt/Protein Kinase B Isoform-specific Expression

Stepwise acetyltransferase association and histone acetylation at the Myod1 locus during myogenic differentiation

Functions of the Proteasome on Chromatin

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