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Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial–facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels., PWWP2A is a chromatin-binding transcriptional regulator that mediates mitosis-progression. Here, the authors provide evidence that PWWP2A directly interacts with H2A.Z nucleosomes, DNA and H3K36me3, binds to an MTA1-specific subcomplex of the NuRD complex (M1HR) and promotes changes to histone acetylation.

Intrinsically disordered proteins (IDPs) are common in eukaryotes. However, relatively few experimental studies have addressed the nature of the rate-limiting transition state for the coupled binding and folding reactions involving IDPs. By using site-directed mutagenesis in combination with kinetics measurements we have here characterized the transition state for binding between the globular TAZ1 domain of CREB binding protein and the intrinsically disordered C-terminal activation domain of Hif-1α (Hif-1α CAD). A total of 17 Hif-1α CAD point-mutations were generated and a Φ-value binding analysis was carried out. We found that native hydrophobic binding interactions are not formed at the transition state. We also investigated the effect the biologically important Hif-1α CAD Asn-803 hydroxylation has on the binding kinetics, and found that the whole destabilization effect due the hydroxylation is within the dissociation rate constant. Thus, the rate-limiting transition state is “disordered-like”, with native hydrophobic binding contacts being formed cooperatively after the rate-limiting barrier, which is clearly shown by linear free energy relationships. The same behavior was observed in a previously characterized TAZ1/IDP interaction, which may suggest common features for the rate-limiting transition state for TAZ1/IDP interactions.

Upplevelsens era är här och ställer samtliga aktörer i samhället inför utmaningar. Upplevelsen ska inte längre bara fylla ett funktionellt behov, den ska beröra konsumenten på ett helt annat sätt. Allt i syfte att kunna erbjuda konsumenten en upplevelse utöver det vanliga för att som företag lyckas med att särskilja sig från sina konkurrenter. En strategi för att lyckas med differentiering är att engagera konsumentens sinnen i upplevelsen. Uppsatsen tar utgångspunkt i två teoretiska begrepp: Pine & Gilmore´s (1999) strategimodell, The Experience Realms, och Hulténs m.fl. (2007) teori om sinnesmarknadsföring. Vårt arbete syftar till att utreda vad som händer i mötet mellan dessa två teorier på ett konkret fält – Orbaden Konferens och Spa. Studien har varit av deduktiv karaktär. Vi har tillämpat kvalitativ metod då vi med utgångspunkt från valda teorier önskat undersöka hur ett spa-besök upplevs av gäster, samt utreda hur en specifik anläggning arbetar med att skapa upplevelser. Vi genomförde fyra kvalitativa intervjuer, två med representanter från Orbaden Konferens och Spa, två med personer som har gedigen erfarenhet av att vara besökare på spa. Då teorin kopplades till empirin kunde flera mötespunkter av vikt urskiljas. Mötespunkterna som framträtt kan vara av avgörande vikt vid skapandet av upplevelser.