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Highlights: [•] PolyQ fibril aggregates exhibit enhanced VCD and supramolecular chiral organization that differ from all previously observed amyloid fibrils. [•] Q ⩾35 aggregates show a further enhanced level of supramolecular chiral organization compared to Q ⩽30 aggregates. [•] Q ⩾35 and Q ⩽30 fibril aggregates exhibit the same secondary structure and VCD intensity pattern. . [ABSTRACT FROM AUTHOR]

Machado–Joseph disease (MJD) is a progressive neurodegenerative disorder caused by expansion of a CAG motif within the translated region of the human MJD (hMJD) gene which has been mapped to chromosome 14q. In this study, the hMJD gene was identified in two overlapping bacterial artificial chromosome (BAC) clones and contained 11 exons resulting in a 6.14 kb transcript. The 5′-flanking region of the hMJD gene included a TATA-less promoter with GC-rich regions, a CCAAT box and multiple potential SP1 binding sites. Luciferase reporter assays performed in neuronal and non-neuronal human cell lines demonstrated a core promoter within the 200 bp region immediately upstream of the putative transcriptional start site (−89 according to the start codon). DNA–protein interactions defined by electrophoretic mobility shift assays (EMSA) revealed specific binding of nuclear proteins to the putative core promoter region. [Copyright &y& Elsevier]

The androgen receptor (AR) is a ligand-dependent transcription factor and belongs to the nuclear receptor family. The AR gene contains a long polymorphic CAG repeat, coding for a polyglutamine tract. In the full size AR, the deletion of the polyglutamine tract results in an increase in the transactivation through canonical AREs. However, this effect is clearly dependent on the response elements, since it is not observed on selective elements. In our assays, a deletion of the repeat positively affected the interactions of the ligand-binding domain with the amino-terminal domain as well as the recruitment of the p160 coactivator SRC-1e to the amino-terminal domain of the AR. This is reflected by an enhanced coactivation of the AR by SRC-1e. [Copyright &y& Elsevier]