title: HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
abstract: BACKGROUND
  Cellular differentiation is characterized by the acquisition of specialized structures and functions, cell cycle exit, and global attenuation of the DNA damage response. It is largely unknown how these diverse cellular events are coordinated at the molecular level during differentiation. We addressed this question in a model system of neuroblastoma cell differentiation induced by HOXC9.
  
  
  RESULTS
  We conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program. Microarray gene expression profiling revealed that HOXC9-induced differentiation was associated with transcriptional regulation of 2,370 genes, characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping by ChIP-seq demonstrated that HOXC9 bound to 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and the DNA damage response. Moreover, we showed that HOXC9 interacted with the transcriptional repressor E2F6 and recruited it to the promoters of cell cycle genes for repressing their expression.
  
  
  CONCLUSIONS
  Our results demonstrate that HOXC9 coordinates diverse cellular processes associated with differentiation by directly activating and repressing the transcription of distinct sets of genes.
authors.affiliation: Cancer Center, Georgia Regents University, Augusta, GA 30912, USA. hcui@swu.edu.cn.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Wang
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Choi
authors.forename: Jane
authors.initials: J
authors.lastname: Ding
authors.forename: Liqun
authors.initials: L
authors.lastname: Yang
authors.forename: Lambert C
authors.initials: LC
authors.lastname: Ngoka
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Zha
authors.forename: Ling
authors.initials: L
authors.lastname: Mao
authors.forename: Bilian
authors.initials: B
authors.lastname: Jin
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Ren
authors.forename: John
authors.initials: J
authors.lastname: Cowell
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Ding
mesh_terms: D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics; D050701:E2F6 Transcription Factor / Q000378:metabolism; D020868:Gene Silencing; D015894:Genome, Human; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D059467:Transcriptome
chemical_list: D050701:E2F6 Transcription Factor; C491744:E2F6 protein, human; D018398:Homeodomain Proteins; C522807:Hoxc9 protein, human