RRC ID 32492
著者 López-Falcón B, Meyer-Nava S, Hernández-Rodríguez B, Campos A, Montero D, Rudiño E, Vázquez M, Zurita M, Valadez-Graham V.
タイトル Characterization of the Drosophila group ortholog to the amino-terminus of the alpha-thalassemia and mental retardation X-Linked (ATRX) vertebrate protein.
ジャーナル PLoS One
Abstract The human ATRX gene encodes hATRX, a chromatin-remodeling protein harboring an helicase/ATPase and ADD domains. The ADD domain has two zinc fingers that bind to histone tails and mediate hATRX binding to chromatin. dAtrx, the putative ATRX homolog in Drosophila melanogaster, has a conserved helicase/ATPase domain but lacks the ADD domain. A bioinformatic search of the Drosophila genome using the human ADD sequence allowed us to identify the CG8290 annotated gene, which encodes three ADD harboring- isoforms generated by alternative splicing. This Drosophila ADD domain is highly similar in structure and in the amino acids which mediate the histone tail contacts to the ADD domain of hATRX as shown by 3D modeling. Very recently the CG8290 annotated gene has been named dadd1. We show through pull-down and CoIP assays that the products of the dadd1 gene interact physically with dAtrxL and HP1a and all of them mainly co-localize in the chromocenter, although euchromatic localization can also be observed through the chromosome arms. We confirm through ChIP analyses that these proteins are present in vivo in the same heterochromatic regions. The three isoforms are expressed throughout development. Flies carrying transheterozygous combinations of the dadd1 and atrx alleles are semi-viable and have different phenotypes including the appearance of melanotic masses. Interestingly, the dAdd1-b and c isoforms have extra domains, such as MADF, which suggest newly acquired functions of these proteins. These results strongly support that, in Drosophila, the atrx gene diverged and that the dadd1-encoded proteins participate with dAtrx in some cellular functions such as heterochromatin maintenance.
巻・号 9(12)
ページ e113182
公開日 2014-12-1
DOI 10.1371/journal.pone.0113182
PII PONE-D-14-31942
PMID 25437195
PMC PMC4249797
MeSH Amino Acid Sequence Animals Cell Line Chromobox Protein Homolog 5 Chromosomal Proteins, Non-Histone / chemistry* Chromosomal Proteins, Non-Histone / metabolism* Conserved Sequence DNA Helicases / chemistry* DNA Helicases / metabolism Drosophila Proteins / chemistry* Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* Gene Expression Regulation, Developmental Heterochromatin / metabolism Humans Models, Molecular Molecular Sequence Data Nuclear Proteins / chemistry* Nuclear Proteins / metabolism Protein Structure, Tertiary Protein Transport Sequence Homology, Amino Acid* X-linked Nuclear Protein
IF 2.74
引用数 5
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ショウジョウバエ NP0793 (DGRC#112334) NP1240 (DGRC#103952 or DGRC#112583) Su(var)205[2] (DGRC#101822)