HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation

Xiangwei Wang, Jeong-Hyeon Choi, Jane Ding, Liqun Yang, Lambert C. Ngoka, Eun J. Lee, Yunhong Zha, Ling Mao, Bilian Jin, Mingqiang Ren, John Kenneth Cowell, Shuang Huang, Huidong Shi, Hongjuan Cui, Hanfei Ding

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Article number830
JournalBMC Genomics
Volume14
Issue number1
DOIs
StatePublished - Nov 25 2013

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cdc Genes
Genes
DNA Damage
Cell Cycle
Chromosome Mapping
Gene Expression Profiling
Neuroblastoma
DNA Repair
Cell Differentiation
Up-Regulation
Down-Regulation
Genome

Keywords

  • Cell cycle arrest
  • DNA damage response
  • E2F6
  • HOXC9
  • Neuroblastoma
  • Neuronal differentiation

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation. / Wang, Xiangwei; Choi, Jeong-Hyeon; Ding, Jane; Yang, Liqun; Ngoka, Lambert C.; Lee, Eun J.; Zha, Yunhong; Mao, Ling; Jin, Bilian; Ren, Mingqiang; Cowell, John Kenneth; Huang, Shuang; Shi, Huidong; Cui, Hongjuan; Ding, Hanfei.

In: BMC Genomics, Vol. 14, No. 1, 830, 25.11.2013.

Research output: Contribution to journalArticle

Wang, Xiangwei ; Choi, Jeong-Hyeon ; Ding, Jane ; Yang, Liqun ; Ngoka, Lambert C. ; Lee, Eun J. ; Zha, Yunhong ; Mao, Ling ; Jin, Bilian ; Ren, Mingqiang ; Cowell, John Kenneth ; Huang, Shuang ; Shi, Huidong ; Cui, Hongjuan ; Ding, Hanfei. / HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation. In: BMC Genomics. 2013 ; Vol. 14, No. 1.
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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.",
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AU - Ngoka, Lambert C.

AU - Lee, Eun J.

AU - Zha, Yunhong

AU - Mao, Ling

AU - Jin, Bilian

AU - Ren, Mingqiang

AU - Cowell, John Kenneth

AU - Huang, Shuang

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AU - Ding, Hanfei

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