Identification And Functional Analysis Of The Basic Helix-loop-helix(bHLH) Transcription Factors In The Meat Cattle

The basic helix-loop-helix(bHLH)transcription factors form a super family of eukaryotic proteins which play central roles in many important developmental processes,such as: cell proliferation and differentiation,neurogenesis,myogenesis,erythropoiesis,intestinal tissue development and sex determination.Cattle is a herbivorous ruminant of mammalian in the artiodactyla order,provide a significant source of milk,meat and leather to humans.The cattle genome contains at least a minimum of 22,000 genes,of which 80% are shared with humans.Cattle genetically similar to humans,far more than mice,and can replace experimental mice as animal models of human disease.The yak can adapt to high altitude environment,manifested in well-developed heart and lung,without pulmonary hypertension,with higher foraging ability and energy metabolism and so on.Genomic comparisons between humans and cattle provide a view to better understand the genetic basis of human disease.The bHLH transcription factors contain a highly conserved domain of approximately 60 amino acids,which comprises basic region(b)and HLH region.The basic domain located at the N-terminus,and half of the residues are basic,which bind to specific hexanucleotide DNA sequences.While the HLH domain located at carboxyl terminal,which contains two helices separated by a variable loop region.The HLH domain of each partner recognizes and brought together through formation of homodimeric or heterodimeric complexes.bHLH transcription factors were classified into six higher-order groups(group A-F)and 45 orthologous families based on the sequence specificity of DNA binding and the characteristics of conserved protein domain.According to the reported genome resources in the NCBI of cattle and yak,we BLAST searches against the cattle and yak genome database to obtaining the bHLH sequence.Performing the bioinformatics methods such as sequence alignment and phylogenetic analysis to systematically identify,classify as well as the evolved and function analyze the bHLH transcription factor family members in the whole genome of domestic cattle and yak.Conclusions are as follows:1.There were 109 bHLH proteins identified in the domestic cattle genome,of which 185 bHLH proteins were predicted protein.Phylogenetic analyses showed that the 251 proteins pertain to the 44 families with 46,25,14,3,13 and 4 members in the higher-order groups A,B,C,D,E and F,respectively,members of Delilah family were not found,4 proteins were categorized as Orphans.There were 102 bHLH proteins identified in the domestic cattle genome.Phylogenetic analyses showed that the 102 proteins pertain to the 43 families with 43,25,16,3,10 and 3 members in the higher-order groups A,B,C,D,E and F,respectively,members of PTFb and Delilah family were not found,two proteins were categorized as Orphans.2.There were multiple protein isoforms in the identified bHLH transcription factor of domestic cattle and yak.The member of Hes gene are more in many organisms whose bHLH transcription factor were identified,but gene Hes3,Hes4 and Hes6 were not found in the yak genome.Besides,we re-named 14 cattle bHLH protein and 9 yak bHLH protein.3.Using the online analysis tools KOBAS,DAVID and STRING to analyze the Gene Ontology(GO)annotations and functional pathways as well as the functional protein association networks,found that the main functional activities of the cattle bHLH transcription factor are protein dimerization activity,DNA binding,transcription regulatory activity and so on.Besides,there are many other functional activities,such as: muscle tissues development and organogenesis,cardiac morphogenesis,neurogenesis,kinds of cell differentiation and aging process.The yak bHLH transcription factor play roles in regulation of transcription,DNA binding,DNA-templated,muscle organ development,neuron development.Both cattle and yak bHLH transcription factor regulate many important signaling pathway,and they participate in various cancers,such as: small cell lung cancer,thyroid cancer,renal cell carcinoma,they also participate in different diseases: maturity onset diabetes of the young,herpes simplex infection,etc.In addition,the yak bHLH transcription factor are related to chemical carcinogenesis.