From: Gotea, Valer (NIH/NLM/NCBI) [E]
Sent: Friday, March 06, 2009 6:04 PM
To: NLM/NCBI List ncbi-seminar
Subject: CBB Seminar: Tuesday, March 10, 11:00, B2 NCBI Library

CBB Seminar
Tuesday, March 10, 2009, 11:00am
Bldg 38A, B2 NCBI Library

Speaker: Valer Gotea


Homotypic clusters of transcription factor binding sites in human
promoters and developmental enhancers

Cis-regulatory modules are often associated with the occurrence of
multiple transcription factor binding sites (TFBS). Clustering of
multiple TFBSs of for the same transcription factor (TF) is a phenomenon
known to occur widely in nature, but the occurrence of such homotypic
clusters of TFBSs (HCTs) in the human genome has remained largely
unknown. In this study we used known binding motifs for vertebrate TFs
(from TRANSFAC and JASPAR databases) and a hidden Markov model-based
approach to detect HCTs in the human, mouse, chicken, and fugu genomes,
and we examined their association with regulatory modules. We found that
evolutionarily conserved HCTs occupy nearly 2% of the human genome
sequence, and their binding sites are subject to negative selection.
More than half of all human gene promoters and known developmental
enhancers contain HCTs. We also found that HCTs are enriched near
transcription factors and developmental genes.  Our results indicate
that HCTs are a common feature of human cis-regulatory modules and
suggest that they play an extensive role in gene regulation in the human
and other vertebrate genomes.


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Valer Gotea
Research Fellow
Ovcharenko Group
CBB / NCBI / NLM / NIH