Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.

Neuronal intermediate filament inclusion disease (NIFID) is a neurodegenerative disorder of a heterogeneous clinical phenotype, encompassing behavioural changes, language impairment, perseveration, executive dysfunction with or without early onset dementia, extrapyramidal features, and subclinical or clinical involvement of upper and lower motor neurons, with age at onset of reported cases ranging from 23 to 56 years (table 1).1–5 NIFID was initially characterised neuropathologically on the basis of intraneuronal cytoplasmic inclusions of variable morphology which immunostained for all class IV intermediate filament (IF) proteins, namely NF-H, NF-M, NF-L and alpha-internexin.1–3 5 More recently it has been shown that a much larger proportion of the inclusions in NIFID are immunoreactive with the fused in sarcoma (FUS) protein than with IF,6 leading to changes in the suggested nomenclature.7 8 We present a further case demonstrating the broad phenotypic features, overlapping with both corticobasal degeneration and motor neuron disease. View this table: Table 1 Approximate frequencies of clinical features in neuronal intermediate filament inclusion disease cases at presentation and follow-up (n=16)1,2,4,5 A 62-year-old right-handed woman presented with a 2-year history of progressive difficulty with coordination and balance. She noticed weak grip and poor coordination in her right hand when playing tennis and had difficulty assembling familiar scuba diving equipment. She developed involuntary twitching of the fingers in the right hand and heaviness in the right arm. Over the next few months asymmetric leg weakness (right > …

A 30-year-old woman presented to her local hospital with an abrupt onset of left-sided headache and retro-orbital pain, dizziness, unsteadiness, vomiting, dysarthria, right facial paresis and right hemiparesis. She was otherwise well, and taking the oral contraceptive pill. MR brain imaging showed high signal intensity in the left pons (fig 1) and MR venography showed evidence of left sigmoid sinus and proximal internal jugular vein thrombosis (figs 2 and 3). She was anticoagulated with unfractionated …

Two siblings fulfilling clinical diagnostic criteria for late-onset Alzheimer's disease (AD) are reported. The family history suggested a total of nine individuals affected with AD in three generations with autosomal dominant disease transmission. Neurogenetic testing of the proband revealed a mutation, R269H, in the presenilin-1 (PS1) gene. Late-onset AD may be associated with deterministic PS1 mutations; these should be sought when the family history suggests autosomal dominant disease transmission.