Neurogenin 3 recruits CBP co-activator to facilitate histone H3/H4 acetylation in the target gene INSM1.
INSM1 is a downstream target gene of neurogenin 3 (ngn3). A promoter construct containing the -426/+40bp region transiently co-transfected into NIH-3T3 cells with a ngn3 expression plasmid resulted in a 12-fold increase in promoter activity. The ngn3/E47 heterodimer selectively binds and activates the E-box3 of the INSM1 promoter. The endogenous ngn3 and CREB-binding protein (CBP) co-activator occupy the INSM1 promoter, resulting in hyper-acetylation of histone H3/H4 chromatin in a human neuroblastoma cell line, IMR-32. Additionally, adenoviral ngn3 can induce endogenous INSM-1 expression in pancreatic ductal carcinoma-1 cells through the recruitment of CBP to the INSM1 promoter and increase the acetylation of the INSM1 promoter region.
Breslin
Mary B
MB
The Research Institute for Children, Children's Hospital in New Orleans, 200 Henry Clay Avenue, Research and Education Building, Rm. 2211, New Orleans, LA 70118, USA.
Wang
Hong-Wei
HW
Pierce
Amy
A
Aucoin
Rebecca
R
Lan
Michael S
MS
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003345:Corticosterone; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D003345:Corticosterone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C477059:Insm1 protein, mouse; C498695:NEUROG3 protein, human; C407737:Neurog3 protein, mouse; C087342:INSM1 protein, human