title: Diversity and complexity in chromatin recognition by TFII-I transcription factors in pluripotent embryonic stem cells and embryonic tissues.
abstract: GTF2I and GTF2IRD1 encode a family of closely related transcription factors TFII-I and BEN critical in embryonic development. Both genes are deleted in Williams-Beuren syndrome, a complex genetic disorder associated with neurocognitive, craniofacial, dental and skeletal abnormalities. Although genome-wide promoter analysis has revealed the existence of multiple TFII-I binding sites in embryonic stem cells (ESCs), there was no correlation between TFII-I occupancy and gene expression. Surprisingly, TFII-I recognizes the promoter sequences enriched for H3K4me3/K27me3 bivalent domain, an epigenetic signature of developmentally important genes. Moreover, we discovered significant differences in the association between TFII-I and BEN with the cis-regulatory elements in ESCs and embryonic craniofacial tissues. Our data indicate that in embryonic tissues BEN, but not the highly homologous TFII-I, is primarily recruited to target gene promoters. We propose a "feed-forward model" of gene regulation to explain the specificity of promoter recognition by TFII-I factors in eukaryotic cells.
authors.affiliation: Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, School of Dentistry, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Aleksandr V
authors.initials: AV
authors.lastname: Makeyev
authors.forename: Badam
authors.initials: B
authors.lastname: Enkhmandakh
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Pujan
authors.initials: P
authors.lastname: Joshi
authors.forename: Dong-Guk
authors.initials: DG
authors.lastname: Shin
authors.forename: Dashzeveg
authors.initials: D
authors.lastname: Bayarsaihan
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; C486330:Gtf2i protein, mouse; D019473:Transcription Factors, TFII