I am writing to inquire if you are interested in having ChIP-chip (mouse
promoter array) data from mouse testis for the transcription factor DMRT1
to distribute as part of you browser. We have a PNAS publication in press
on this and have tracks from three independent IP experiments. We will be
including the tracks on a interactive web site that will be freely
available to readers but thought you might want to host the tracks as well.
The abstract of the paper is copied below.
We need a quick answer as we need to return the proofs today and need
to know whether to say the tracks will be available on your genome browser.
Our web site will be up and running later today and I can provide you
with a URL if you are interested.
Thank you for your consideration of this matter.
Vivian Bardwell
Genome wide analysis of DNA binding and transcriptional regulation by the
mammalian Doublesex homolog DMRT1 in the juvenile testis
Mark M. Murphy1, Aaron L. Sarver2, Daren Rice3, Katerina Hatzi4, Kenny Ye5,
Ari Melnick4, Leslie L. Heckert3, David Zarkower1, Vivian J. Bardwell1*
ABSTRACT
Doublesex- and MAB-3-related transcription factors (DM domain
proteins) are widely conserved in metazoan sex determination and sexual
differentiation. One of these proteins, DMRT1, plays diverse and essential
roles in development of the vertebrate testis. In mammals DMRT1 is
expressed and required in both germ cells and their supporting Sertoli
cells. Despite its critical role in testicular development little is known
of how DMRT1 functions as a transcription factor or what genes it binds and
regulates. Here we combine chromatin immunoprecipitation methods with
conditional gene targeting and mRNA expression analysis. This identified
almost 1400 promoter-proximal regions bound by DMRT1 in the juvenile mouse
testis and determined how expression of the associated mRNAs is affected
when Dmrt1 is selectively mutated in germ cells or Sertoli cells. These
analyses revealed that DMRT1 is a bifunctional transcriptional regulator,
activating some genes and repressing others. ChIP analysis using
conditional mutant testes showed that DNA binding and transcriptional
regulation of individual target genes can differ between germ cells and
Sertoli cells. Genes bound by DMRT1 in vivo were enriched for a motif
closely resembling the sequence DMRT1 prefers in vitro. Differential
response of genes to loss of DMRT1 corresponded to differences in the
enriched motif, suggesting that other trans-acting factors may modulate
DMRT1 activity. DMRT1 bound its own promoter and those of six other Dmrt
genes, indicating auto- and cross regulation of these genes. Many of the
DMRT1 target genes identified here are known to be important for a variety
of functions in testicular development; the others are candidates for
further investigation.
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