Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression

Shakur Mohibi, Channabasavaiah B Gurumurthy, Alo Nag, Jun Wang, Sameer Mirza, Yousaf Mian, Meghan Quinn, Bryan Katafiasz, James D Eudy, Sanjit Pandey, Chittibabu Guda, Mayumi Naramura, Hamid Band, Vimla Band

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Ada3 protein is an essential component of histone acetyl transferase containing coactivator complexes conserved from yeast to human. We show here that germline deletion of Ada3 in mouse is embryonic lethal, and adenovirus-Cre mediated conditional deletion of Ada3 in Ada3FL/FL mouse embryonic fibroblasts leads to a severe proliferation defect which was rescued by ectopic expression of human Ada3. A delay in G1 to S phase of cell cycle was also seen that was due to accumulation of Cdk inhibitor p27 which was an indirect effect of c-myc gene transcription control by Ada3. We further showed that this defect could be partially reverted by knocking down p27. Additionally, drastic changes in global histone acetylation and changes in global gene expression were observed in microarray analyses upon loss of Ada3. Lastly, formation of abnormal nuclei, mitotic defects and delay in G2/M to G1 transition was seen in Ada3 deleted cells. Taken together, we provide evidence for a critical role of Ada3 in embryogenesis and cell cycle progression as an essential component of HAT complex.

Original languageEnglish (US)
Pages (from-to)29442-29456
Number of pages15
JournalJournal of Biological Chemistry
Volume287
Issue number35
DOIs
StatePublished - Aug 24 2012

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Histones
Embryonic Development
Cell Cycle
Chemical activation
Cells
myc Genes
Microarray Analysis
Acetylation
Transferases
S Phase
Adenoviridae
Fibroblasts
Yeasts
Gene Expression
Defects
Proteins
Transcription
Microarrays
Gene expression
Yeast

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression. / Mohibi, Shakur; Gurumurthy, Channabasavaiah B; Nag, Alo; Wang, Jun; Mirza, Sameer; Mian, Yousaf; Quinn, Meghan; Katafiasz, Bryan; Eudy, James D; Pandey, Sanjit; Guda, Chittibabu; Naramura, Mayumi; Band, Hamid; Band, Vimla.

In: Journal of Biological Chemistry, Vol. 287, No. 35, 24.08.2012, p. 29442-29456.

Research output: Contribution to journalArticle

Mohibi, Shakur ; Gurumurthy, Channabasavaiah B ; Nag, Alo ; Wang, Jun ; Mirza, Sameer ; Mian, Yousaf ; Quinn, Meghan ; Katafiasz, Bryan ; Eudy, James D ; Pandey, Sanjit ; Guda, Chittibabu ; Naramura, Mayumi ; Band, Hamid ; Band, Vimla. / Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 35. pp. 29442-29456.
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