Inducers of gamma globin gene expression and screening assays therefor

An isolated nucleic acid molecule comprising a human gamma globin gene promoter operatively linked upstream of a reporter gene, wherein the human gamma globin gene promoter has a 5' terminus at position -140 relative to the start site of transcription of the human gamma globin gene, wherein sequences in said nucleic acid molecule upstream of said position -140 are not human gamma globin promoter sequences.

An isolated nucleic acid molecule comprising a human gamma globin gene promoter operatively linked upstream of a reporter gene, wherein the human gamma globin gene promoter has a 5' terminus at position -1200 relative to the start site of transcription of the human gamma globin gene, wherein sequences in said nucleic acid molecule upstream of said position -1200 are not human gamma globin promoter sequences.

An isolated nucleic acid molecule comprising a human gamma globin gene 3' enhancer operatively linked downstream of a reporter gene.

A method for identifying an agent that stimulates gamma globin gene expression in a mammalian cell, comprising:

• a) contacting a mammalian cell with an agent to be tested, wherein a nucleic acid molecule comprising a human gamma globin gene 3' enhancer operatively linked downstream of a reporter gene has been introduced into the mammalian cell;
• and
• b) measuring reporter gene activity in the mammalian cell, wherein an increase in reporter gene activity in the presence of the agent, relative to reporter gene activity in the absence of the agent, is indicative that the agent stimulates gamma globin gene expression.

A method for identifying an agent that enhances stimulation of gamma globin gene expression by a short chain fatty acid, comprising:

• a) contacting a mammalian cell with an agent to be tested and with a short chain fatty acid, wherein a nucleic acid molecule comprising a regulatory region of a gamma globin gene operatively linked to a reporter gene has been introduced into the mammalian cell;
• and
• b) measuring reporter gene activity in the mammalian cell, wherein an increase in reporter gene activity in the presence of the agent, relative to reporter gene activity in the absence of the agent, is indicative that the agent enhances stimulation of gamma globin gene expression by a short chain fatty acid.