PCAF plays a role in transcriptional activation, cell-cycle arrest, and cell differentiation in cultured cells. PCAF contributes to transcriptional activation by acetylating chromatin and transcription factors through its intrinsic histone acetylase activity. In this report, we present evidence for the in vivo function of PCAF and the closely related PCAF-B͞GCN5. Mice lacking PCAF are developmentally normal without a distinct phenotype. In PCAF null-zygous mice, protein levels of PCAF-B͞GCN5 are drastically elevated in lung and liver, where PCAF is abundantly expressed in wild-type mice, suggesting that PCAF-B͞GCN5 functionally compensates for PCAF. In contrast, animals lacking PCAF-B͞GCN5 die between days 9.5 and 11.5 of gestation. Normally, PCAF-B͞GCN5 mRNA is expressed at high levels already by day 8, whereas PCAF mRNA is first detected on day 12.5, which may explain, in part, the distinct knockout phenotypes. These results provide evidence that PCAF and PCAF-B͞GCN5 play distinct but functionally overlapping roles in embryogenesis.H uman (h)PCAF (p300͞CBP associated factor; ref. 1) is a transcriptional coactivator with intrinsic histone acetylase activity, which contributes to transcriptional activation by modifying chromatin and transcriptional factors (for reviews, see refs. 2-5). Although an exact mechanism of how acetylation of histones contribute to transcriptional activation has not been clarified, it has been thought that acetylation of nucleosomal histones leads to relaxation of chromatin structure such that various transcription factors can gain access and function onto chromatin DNA. Although histones are physiologically relevant substrates for PCAF, PCAF also acetylates transcriptional activators p53 (6, 7) and MyoD (8), as originally demonstrated by p300 acetylase (9), and stimulates DNA binding.PCAF is present in a stable multisubunit complex consisting of more than 20 distinct polypeptides, whose molecular masses range from 10 to 400 kDa (10). Although recombinant PCAF per se cannot efficiently acetylate histones in nucleosomal contexts, the PCAF complex that we purified can, strongly suggesting that subunits in the PCAF complex could stimulate acetylation of relevant substrates (10). Moreover, characterization of subunits of the PCAF complex has revealed that they are TATA boxbinding protein-associated factors (TAFs), which were originally found in TFIID; TAF-related PAF65␣ and ␤; human homologs of yeast transcriptional cofactors ADA2, ADA3, and Spt3 as well as PAF400, which exhibits sequence similarity to members of the ATM superfamily (10, 11). Importantly, TAF80, TAF-like PAF65␣, and TAF20͞15 bear sequence similarities to core histones (10) and thus may form a histone octamer-like structure in the PCAF complex, as has been proposed for TFIID (12)(13)(14). Furthermore, TAF-like PAF65␤ has WD40-repeats, motifs often found in factors that target chromatin (10).The second family member is hPCAF-B͞GCN5 (5, 15). PCAF and PCAF-B͞GCN5 are well conserved over their entire sequence, and both exhibit p...

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Background Atopic dermatitis (AD) is an allergic disease that affects individuals of various ages. Recently, the IL‐4/13 inhibitor dupilumab has gained regulatory approval for clinical use in AD patients. Dupilumab has been reported to reduce several markers of AD, including the serum levels of thymus and activation‐regulated chemokine (TARC/CCL17), blood lactate dehydrogenase (LDH), and serum total immunoglobulin E (IgE). Methods We retrospectively reviewed data from 40 AD patients who were treated with dupilumab. Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), body surface area (BSA) scores, TARC, LDH, total IgE, and eosinophil count in peripheral blood were assessed for a total of 32 weeks. Results The EASI, IGA, and BSA scores improved significantly with treatment, indicating a reduction in AD severity. Serum TARC and LDH levels also significantly decreased with treatment. Serum IgE levels were unchanged at 2 weeks of treatment but decreased significantly between 4 and 32 weeks. The number of eosinophils in the peripheral blood decreased at 4, 16, and 32 weeks after treatment initiation. Conclusions Several studies have reported that serum TARC, LDH, and total IgE levels are reduced by dupilumab treatment. Our real‐world data are the first to demonstrate a reduction in blood eosinophilia in patients who receive clinical treatment with dupilumab.