Microcephaly-Thin Corpus Callosum Syndrome Maps to 8q23.2-q24.12
PEDIATRIC NEUROLOGY
Authors: Halevy, Ayelet; Basel-Vanagaite, Lina; Shuper, Avinoam; Heiman, Shlomit; Har-Zahav, Adi; Birk, Efrat; Maya, Idit; Kornreich, Liora; Inbar, Dov; Nuernberg, Gudrun; Nuernberg, Peter; Steinberg, Tamar; Straussberg, Rachel
Abstract
Postnatal microcephaly is defined as normal head circumference at birth, which progressively declines to more than 2 standard deviations below the average for the patient's age and sex. We describe four patients from three consanguineous families of Arab Bedouin origin who presented with autosomal recessive inheritance of progressive microcephaly, spasticity, thin corpus callosum, pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping Nspl 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2-q24.12. The candidate region includes 22 known or predicted genes, including RAD21, which is related to the cohesion complex EIF3H, which is involved in translation initiation, and TAF2, which may be involved in intellectual disability. Identification of the causative gene in our reported family will shed light on the pathogenesis of this severe condition. (C) 2012 Elsevier Inc. All rights reserved.
Mapping the Initiator Binding Taf2 Subunit in the Structure of Hydrated Yeast TFIID
STRUCTURE
Authors: Papai, Gabor; Tripathi, Manish K.; Ruhlmann, Christine; Werten, Sebastiaan; Crucifix, Corinne; Weil, P. Anthony; Schultz, Patrick
Abstract
The general transcription factor TFIID is a large multi-subunit complex required for the transcription of most protein-encoding genes by RNA polymerase II. Taking advantage of a TFIIID preparation partially depleted in the initiator-binding Taf2p subunit, we determined the conformational and biochemical variations of the complex by electron tomography and cryo-electron microscopy of single molecules. Image analysis revealed the extent of conformational flexibility of the complex and the selection of the most homogeneous TFIID subpopulation allowed us to determine an improved structural model at 23 angstrom resolution. This study also identified two subpopulations of Taf2p-containing and Taf2p-depleted TFIID molecules. By comparing these two TFIID species we could infer the position of Taf2p, which was confirmed by immunolabeling using a subunit-specific antibody. Mapping the position of this crucial subunit in the vicinity of Taf1p and of TBP sheds new light on its role in promoter recognition.