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Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos.

Scientific reports | 2016

PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.

Pubmed ID: 27412763 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


NCBI BLAST (tool)

RRID:SCR_004870

Web search tool to find regions of similarity between biological sequences. Program compares nucleotide or protein sequences to sequence databases and calculates statistical significance. Used for identifying homologous sequences.

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Staden Package (tool)

RRID:SCR_005629

A fully developed set of DNA sequence assembly (Gap4 and Gap5), editing and analysis tools (Spin) for Unix, Linux, MacOSX and MS Windows.

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InterPro (tool)

RRID:SCR_006695

Service providing functional analysis of proteins by classifying them into families and predicting domains and important sites. They combine protein signatures from a number of member databases into a single searchable resource, capitalizing on their individual strengths to produce a powerful integrated database and diagnostic tool. This integrated database of predictive protein signatures is used for the classification and automatic annotation of proteins and genomes. InterPro classifies sequences at superfamily, family and subfamily levels, predicting the occurrence of functional domains, repeats and important sites. InterPro adds in-depth annotation, including GO terms, to the protein signatures. You can access the data programmatically, via Web Services. The member databases use a number of approaches: # ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST. # PROSITE patterns: provider of simple regular expressions. # PROSITE and HAMAP profiles: provide sequence matrices. # PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs). # PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs). Your contributions are welcome. You are encouraged to use the ''''Add your annotation'''' button on InterPro entry pages to suggest updated or improved annotation for individual InterPro entries.

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A plasmid Editor (tool)

RRID:SCR_014266

Software tool for plasmid and sequence editing, annotating and drawing plasmid sequences. Used to view circular or linear maps of DNA sequences. Users can perform virtual digests whereby they select predefined DNA ladder, or specify their own, and visualize theoretical DNA fragments. Used to highlight restriction sites in editing window, accurately reflect Dam/Dcm blocking of enzyme sites, highlighting and drawing graphic maps using feature annotations from genbank and embl files, highlighting text using pre-defined and custom feature libraries, and directly BLASTing selected sequence at NCBI or Wormbase. Runs across Windows, OS X, and Linux/Unix.

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European Molecular Biology Laboratory (tool)

RRID:SCR_004473

Intergovernmental organisation funded by public research money from its member states in Europe. Groups and laboratories perform basic research in molecular biology and molecular medicine, training for scientists, students and visitors. Provides development of services, new instruments and methods, data and technology in its member states.

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BLASTX (tool)

RRID:SCR_001653

Web application to search protein databases using a translated nucleotide query. Translated BLAST services are useful when trying to find homologous proteins to a nucleotide coding region. Blastx compares translational products of the nucleotide query sequence to a protein database. Because blastx translates the query sequence in all six reading frames and provides combined significance statistics for hits to different frames, it is particularly useful when the reading frame of the query sequence is unknown or it contains errors that may lead to frame shifts or other coding errors. Thus blastx is often the first analysis performed with a newly determined nucleotide sequence and is used extensively in analyzing EST sequences. This search is more sensitive than nucleotide blast since the comparison is performed at the protein level.

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SAMstrt (tool)

RRID:SCR_001780

Software package that provides the significance analysis of sequencing data with spike-in normalization. The statistical backgrounds and the benefits depend on SAMseq of the samr package.

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SAMTOOLS (tool)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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RefSeq (tool)

RRID:SCR_003496

Collection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.

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Clontech (tool)

RRID:SCR_004423

An Antibody supplier

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BEDTools (tool)

RRID:SCR_006646

A powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.

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BLAT (tool)

RRID:SCR_011919

Software designed to quickly find sequences of 95% and greater similarity of length 25 bases or more.

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TopHat (tool)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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Cufflinks (tool)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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