Pit-1beta reduces transcription and CREB-binding protein recruitment in a DNA context-dependent manner.
Many transcription factors are expressed as multiple isoforms with distinct effects on the regulation of gene expression, and the functional consequences of structural differences between transcription factor isoforms may allow for precise control of gene expression. The pituitary transcription factor isoforms Pit-1 and Pit-1beta differentially regulate anterior pituitary hormone gene expression. Pit-1 is required for the development of and appropriate hormone expression by anterior pituitary somatotrophs and lactotrophs. Pit-1beta differs structurally from Pit-1 by the splice-insertion of the 26-residue beta-domain in the trans-activation domain, and it differs functionally from Pit-1 in that it represses expression of the prolactin promoter in a cell-type specific manner. In order to identify signal and promoter context requirements for repression by Pit-1beta, we examined its function in the presence of physiological regulatory signals as well as wild-type and mutant Pit-1-dependent target promoters. Here, we demonstrate that Pit-1beta impairs recruitment of cAMP response element-binding protein (CREB)-binding protein to the promoters that it represses. In addition, we show that repression of target promoter activity, reduction in promoter histone acetylation, and decrease of CREB-binding protein recruitment all depend on promoter context. These findings provide a mechanism for promoter-specific repression by Pit-1beta.
Ferry
A L
AL
Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
Locasto
D M
DM
Meszaros
L B
LB
Bailey
J C
JC
Jonsen
M D
MD
Brodsky
K
K
Hoon
C J
CJ
Gutierrez-Hartmann
A
A
Diamond
S E
SE
D000107:Acetylation; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D050882:CREB-Binding Protein; D045744:Cell Line, Tumor; D002843:Chromatin; D004268:DNA-Binding Proteins / Q000502:physiology*; D018274:Electroporation; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000502:physiology*; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C494186:Pou1f1 protein, rat; D020033:Protein Isoforms; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin; D013006:Growth Hormone; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat