Functional Analysis of Hif1 Histone Chaperone in Saccharomyces cerevisiae

G3: Genes, Genomes, Genetics

article

Nora S. Dannah¹  Syed Nabeel-Shah¹  Christoph F. Kurat²  Sarah A. Sabatinos¹  Jeffrey Fillingham¹ 

[1] Department of Chemistry and Biology, Ryerson University, 350 Victoria St., Toronto, M5B, 2K3 Canada;Molecular Biology Division, Biomedical Center, Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany

关键词: Key words: H3/H4 chaperone;    NASP;    chromatin;    Asf1;    SHNi TPR;    Hif1p;    Hat1;   

DOI  :  10.1534/g3.118.200229

学科分类：社会科学、人文和艺术（综合）

来源: Genetics Society of America

【 摘 要 】

The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily conserved H3/H4-specific chaperone and a subunit of the nuclear Hat1 complex that catalyzes the acetylation of newly synthesized histone H4. Hif1 , as well as its human homolog NASP, has been implicated in an array of chromatin-related processes including histone H3/H4 transport, chromatin assembly and DNA repair. In this study, we elucidate the functional aspects of Hif1 . Initially we establish the wide distribution of Hif1 homologs with an evolutionarily conserved pattern of four tetratricopeptide repeats (TPR) motifs throughout the major fungal lineages and beyond. Subsequently, through targeted mutational analysis, we demonstrate that the acidic region that interrupts the TPR2 is essential for Hif1 physical interactions with the Hat1/Hat2-complex, Asf1 , and with histones H3/H4. Furthermore, we provide evidence for the involvement of Hif1 in regulation of histone metabolism by showing that cells lacking HIF1 are both sensitive to histone H3 over expression, as well as synthetic lethal with a deletion of histone mRNA regulator LSM1 . We also show that a basic patch present at the extreme C-terminus of Hif1 is essential for its proper nuclear localization. Finally, we describe a physical interaction with a transcriptional regulatory protein Spt2 , possibly linking Hif1 and the Hat1 complex to transcription-associated chromatin reassembly. Taken together, our results provide novel mechanistic insights into Hif1 functions and establish it as an important protein in chromatin-associated processes.

【 授权许可】

CC BY|CC BY-NC