From: Marino-Ramirez, Leonardo (NIH/NLM/NCBI) [E]
Sent: Monday, June 04, 2007 12:06 PM
To: NLM/NCBI List ncbi-seminar
Subject: CBB seminar, June 5th at 11 AM, B2 Library room

Title: Evolution of cis-regulatory elements in core histone genes
Speaker: Leonardo Mariño-Ramírez
Date: June 5, 2007
Time: 11AM
Location: Bldg. 38A, B2 library

Abstract: Accurate genome-wide identification of cis-regulatory elements requires a combination of computational and experimental approaches.  The growing availability of genomic sequences from numerous eukaryotic species, combined with experimental data on gene regulation, is providing new opportunities to study the evolution of cis-regulatory elements.  The four core histone genes encode the proteins that together with DNA form the nucleosome, the fundamental unit of eukaryotic chromatin.  Core histone genes are often transcribed from bi-directional promoters, facilitating detection of regulatory elements across sequenced eukaryotic genomes.  Their primary sequence and gene expression patterns are both evolutionarily conserved showing from the yeast Saccharomyces cerevisiae to human. We evaluated the evolutionary dynamics of the specific regulatory mechanisms that give rise to the conserved histone regulatory phenotype.  In contrast to the conservation of core histone gene expression patterns, the core histone regulatory machinery has changed greatly among eukaryotic evolutionary lineages. We show that there has been substantial turnover of cis-regulatory elements along with the transcription factors that bind them for fungi, plants, insects and mammals.  This suggests that regulatory mechanisms have been constantly reinvented along different evolutionary lineages.  Additionally, we show evidence that within evolutionary lineages different core histone gene families employ basically the same regulatory machinery.  The presence of lineage-specific histone regulatory mechanisms is opposite to what is seen at the protein sequence level.  Consequently, the regulatory machinery has changed significantly between evolutionarily lineages and little changes have occurred within lineages.  Core histone proteins are more similar within families, irrespective of their species of origin, than between families, consistent with the shared common ancestry of the members of individual histone families.  Structure and sequence comparisons between histone families reveal that H2A and H2B form one related group as do H3 and H4, which is consistent with the nucleosome assembly dynamics.  These results reveal how the plasticity of cis-regulatory elements can contribute maintain an evolutionary conserved gene expression phenotype.

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Leonardo Mariño-Ramírez, Ph.D.
Staff Scientist
NCBI, NLM, NIH
Building 38A, Room 6S614M
8600 Rockville Pike
Bethesda, MD 20894
Voice: (301) 402-3708
Fax: (301) 480-2288
http://ncbi.nih.gov/CBBresearch/Marino/