Transcription factor with 2 activation sites??? (fwd)

Jacobs "G." ghj at mrc-lmb.cam.ac.uk
Sat Dec 19 13:17:16 EST 1992

Forwarded message:
>From @dlgm.dl.ac.uk:bionet-news at dl.ac.uk Sat Dec 19 10:48:07 1992
>Date: Sat, 19 Dec 92 10:26:04 UT
>Message-Id: <921219102604.MIN-LFBAa26371.bionet-news at uk.ac.daresbury>
>From: mangalam at SALK-SC2.SDSC.EDU (Harry Mangalam)
>Reply-To: mangalam at SALK-SC2.SDSC.EDU (Harry Mangalam)
>Sender: "bionet.molbio.proteins mail newsgroup" <bionet-news at dl.ac.uk>
>To: "bionet.molbio.proteins mail newsgroup" <bionet-news at dl.ac.uk>
>Subject: Re: Transcription factor with 2 activation sites???
>X-Article-Number: bionet.molbio.proteins Msg # 139
>Comments: List problems/queries to <biosci at daresbury.ac.uk>
>Comments: To mail both the group and netnews send to (proteins at daresbury.ac.uk)
>Rich Friedman writes:
>>I am wondering if anyone has heard of a transcription factor which has two
>>activation sites.  I am trying to find out if a factor which binds to an
>>enhancer sequence, has the ability to stimulate expression from two promoters,
>>simultaneously.  I think that this would require that the factor would have to
>>have two activation sites.  If you any info, please e-mail me .
>   There are some transcription factors (TFs) that have multiple DNA
>binding domains - Mike Levine's lab characterized one (the name escapes me
>at the moment but I could look it up) that had both a "paired" box and a
>homeobox (homoeobox for the Brits) and both could bind to completely
>different (although in their original work, overlapping) sites.  Recently,
>TFs have been cloned which have large numbers of Zn fingers (>15), many of
>which seem to be capable of binding DNA, and also recently someone cloned a
>monster that had multiple homeoboxes AND multiple Zn fingers.
>   If your question is whether a TF with only one DNA binding site can
>activate multiple genes, then the answer is also yes, with examples too
>numerous to cover.  A favorite example is the anterior pituitary-specific
>Pit1 (aka (if inaccurately) as GHF1) which can activate transcription from
>both the Prolactin promoter (and in fact is absolutely required for PRL
>expression), Growth Hormone promoter (less tightly regulated than PRL), and
>TSH gene, as well as its own promoter (all anterior pituitary-specific
>Hope this is of some help
>Harry Mangalam                                   Vox:(619) 453-4100, x250
>Dept of Biocomputing                                   Fax:(619) 552-1546
>The Salk Institute                        1'   mangalam at salk-sc2.sdsc.edu
>10010 N Torrey Pines Rd                   2'        hjm at salk-sgi.sdsc.edu
>La Jolla CA 92037                         3'         mangalam at salk.bitnet
Just to add to the confusion, at least some of the DNA proteins with
more than one DNA binding domain can select between them via alt.
splicing. This could appear as activating at two different sites in
some assays I guess (I'm not an experimentalist, but it does seem an
obvious point...).
I could give you some examples later (I'm not at my lab. at the 
A point for myself is to distinguish between whether the protein binds
the two promoters *AT THE SAME TIME* or whether it is able to bind
the two promoters, but independently. Two very different things!

Grant Jacobs
MRC Laboratory of Molecular Biology
Hillls Road 
Cambridge CB3 9EU

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