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All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues

BACKGROUND: The promoters of housekeeping genes are well-bound by RNA polymerase II (RNAP) in different tissues. Although the promoters of these genes are known to contain CpG islands, the specific DNA sequences that are associated with high RNAP binding to housekeeping promoters has not been descri...

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Autores principales: Rozenberg, Julian M, Shlyakhtenko, Andrey, Glass, Kimberly, Rishi, Vikas, Myakishev, Maxim V, FitzGerald, Peter C, Vinson, Charles
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267717/
https://www.ncbi.nlm.nih.gov/pubmed/18252004
http://dx.doi.org/10.1186/1471-2164-9-67
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author Rozenberg, Julian M
Shlyakhtenko, Andrey
Glass, Kimberly
Rishi, Vikas
Myakishev, Maxim V
FitzGerald, Peter C
Vinson, Charles
author_facet Rozenberg, Julian M
Shlyakhtenko, Andrey
Glass, Kimberly
Rishi, Vikas
Myakishev, Maxim V
FitzGerald, Peter C
Vinson, Charles
author_sort Rozenberg, Julian M
collection PubMed
description BACKGROUND: The promoters of housekeeping genes are well-bound by RNA polymerase II (RNAP) in different tissues. Although the promoters of these genes are known to contain CpG islands, the specific DNA sequences that are associated with high RNAP binding to housekeeping promoters has not been described. RESULTS: ChIP-chip experiments from three mouse tissues, liver, heart ventricles, and primary keratinocytes, indicate that 94% of promoters have similar RNAP binding, ranging from well-bound to poorly-bound in all tissues. Using all 8-base pair long sequences as a test set, we have identified the DNA sequences that are enriched in promoters of housekeeping genes, focusing on those DNA sequences which are preferentially localized in the proximal promoter. We observe a bimodal distribution. Virtually all sequences enriched in promoters with high RNAP binding values contain a CpG dinucleotide. These results suggest that only transcription factor binding sites (TFBS) that contain the CpG dinucleotide are involved in RNAP binding to housekeeping promoters while TFBS that do not contain a CpG are involved in regulated promoter activity. Abundant 8-mers that are preferentially localized in the proximal promoters and exhibit the best enrichment in RNAP bound promoters are all variants of six known CpG-containing TFBS: ETS, NRF-1, BoxA, SP1, CRE, and E-Box. The frequency of these six DNA motifs can predict housekeeping promoters as accurately as the presence of a CpG island, suggesting that they are the structural elements critical for CpG island function. Experimental EMSA results demonstrate that methylation of the CpG in the ETS, NRF-1, and SP1 motifs prevent DNA binding in nuclear extracts in both keratinocytes and liver. CONCLUSION: In general, TFBS that do not contain a CpG are involved in regulated gene expression while TFBS that contain a CpG are involved in constitutive gene expression with some CpG containing sequences also involved in inducible and tissue specific gene regulation. These TFBS are not bound when the CpG is methylated. Unmethylated CpG dinucleotides in the TFBS in CpG islands allow the transcription factors to find their binding sites which occur only in promoters, in turn localizing RNAP to promoters.
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spelling pubmed-22677172008-03-17 All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues Rozenberg, Julian M Shlyakhtenko, Andrey Glass, Kimberly Rishi, Vikas Myakishev, Maxim V FitzGerald, Peter C Vinson, Charles BMC Genomics Research Article BACKGROUND: The promoters of housekeeping genes are well-bound by RNA polymerase II (RNAP) in different tissues. Although the promoters of these genes are known to contain CpG islands, the specific DNA sequences that are associated with high RNAP binding to housekeeping promoters has not been described. RESULTS: ChIP-chip experiments from three mouse tissues, liver, heart ventricles, and primary keratinocytes, indicate that 94% of promoters have similar RNAP binding, ranging from well-bound to poorly-bound in all tissues. Using all 8-base pair long sequences as a test set, we have identified the DNA sequences that are enriched in promoters of housekeeping genes, focusing on those DNA sequences which are preferentially localized in the proximal promoter. We observe a bimodal distribution. Virtually all sequences enriched in promoters with high RNAP binding values contain a CpG dinucleotide. These results suggest that only transcription factor binding sites (TFBS) that contain the CpG dinucleotide are involved in RNAP binding to housekeeping promoters while TFBS that do not contain a CpG are involved in regulated promoter activity. Abundant 8-mers that are preferentially localized in the proximal promoters and exhibit the best enrichment in RNAP bound promoters are all variants of six known CpG-containing TFBS: ETS, NRF-1, BoxA, SP1, CRE, and E-Box. The frequency of these six DNA motifs can predict housekeeping promoters as accurately as the presence of a CpG island, suggesting that they are the structural elements critical for CpG island function. Experimental EMSA results demonstrate that methylation of the CpG in the ETS, NRF-1, and SP1 motifs prevent DNA binding in nuclear extracts in both keratinocytes and liver. CONCLUSION: In general, TFBS that do not contain a CpG are involved in regulated gene expression while TFBS that contain a CpG are involved in constitutive gene expression with some CpG containing sequences also involved in inducible and tissue specific gene regulation. These TFBS are not bound when the CpG is methylated. Unmethylated CpG dinucleotides in the TFBS in CpG islands allow the transcription factors to find their binding sites which occur only in promoters, in turn localizing RNAP to promoters. BioMed Central 2008-02-05 /pmc/articles/PMC2267717/ /pubmed/18252004 http://dx.doi.org/10.1186/1471-2164-9-67 Text en Copyright © 2008 Rozenberg et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rozenberg, Julian M
Shlyakhtenko, Andrey
Glass, Kimberly
Rishi, Vikas
Myakishev, Maxim V
FitzGerald, Peter C
Vinson, Charles
All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
title All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
title_full All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
title_fullStr All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
title_full_unstemmed All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
title_short All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
title_sort all and only cpg containing sequences are enriched in promoters abundantly bound by rna polymerase ii in multiple tissues
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267717/
https://www.ncbi.nlm.nih.gov/pubmed/18252004
http://dx.doi.org/10.1186/1471-2164-9-67
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