Cargando…
A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding
The c-Myb protein is a transcriptional regulator initially identified by homology to the v-Myb oncoprotein, and has since been implicated in human cancer. The most highly conserved portion of the c-Myb protein is the DNA-binding domain which consists of three imperfect repeats. Many other proteins c...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2008
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572630/ https://www.ncbi.nlm.nih.gov/pubmed/18840288 http://dx.doi.org/10.1186/1476-4598-7-77 |
_version_ | 1782160264057061376 |
---|---|
author | Ko, Emily Ray Ko, Dennis Chen, Carolyn Lipsick, Joseph S |
author_facet | Ko, Emily Ray Ko, Dennis Chen, Carolyn Lipsick, Joseph S |
author_sort | Ko, Emily Ray |
collection | PubMed |
description | The c-Myb protein is a transcriptional regulator initially identified by homology to the v-Myb oncoprotein, and has since been implicated in human cancer. The most highly conserved portion of the c-Myb protein is the DNA-binding domain which consists of three imperfect repeats. Many other proteins contain one or more Myb-related domains, including a number of proteins that do not bind directly to DNA. We performed a phylogenetic analysis of diverse classes of Myb-related domains and discovered a highly conserved patch of acidic residues common to all Myb-related domains. These acidic residues are positioned in the first of three alpha-helices within each of the three repeats that comprise the c-Myb DNA-binding domain. Interestingly, these conserved acidic residues are present on a surface of the protein which is distinct from that which binds to DNA. Alanine mutagenesis revealed that the acidic patch of the third c-Myb repeat is essential for transcriptional activity, but neither for nuclear localization nor DNA-binding. Instead, these acidic residues are required for efficient chromatin binding and interaction with the histone H4 N-terminal tail. |
format | Text |
id | pubmed-2572630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25726302008-10-25 A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding Ko, Emily Ray Ko, Dennis Chen, Carolyn Lipsick, Joseph S Mol Cancer Research The c-Myb protein is a transcriptional regulator initially identified by homology to the v-Myb oncoprotein, and has since been implicated in human cancer. The most highly conserved portion of the c-Myb protein is the DNA-binding domain which consists of three imperfect repeats. Many other proteins contain one or more Myb-related domains, including a number of proteins that do not bind directly to DNA. We performed a phylogenetic analysis of diverse classes of Myb-related domains and discovered a highly conserved patch of acidic residues common to all Myb-related domains. These acidic residues are positioned in the first of three alpha-helices within each of the three repeats that comprise the c-Myb DNA-binding domain. Interestingly, these conserved acidic residues are present on a surface of the protein which is distinct from that which binds to DNA. Alanine mutagenesis revealed that the acidic patch of the third c-Myb repeat is essential for transcriptional activity, but neither for nuclear localization nor DNA-binding. Instead, these acidic residues are required for efficient chromatin binding and interaction with the histone H4 N-terminal tail. BioMed Central 2008-10-07 /pmc/articles/PMC2572630/ /pubmed/18840288 http://dx.doi.org/10.1186/1476-4598-7-77 Text en Copyright © 2008 Ko 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 Ko, Emily Ray Ko, Dennis Chen, Carolyn Lipsick, Joseph S A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding |
title | A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding |
title_full | A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding |
title_fullStr | A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding |
title_full_unstemmed | A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding |
title_short | A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding |
title_sort | conserved acidic patch in the myb domain is required for activation of an endogenous target gene and for chromatin binding |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572630/ https://www.ncbi.nlm.nih.gov/pubmed/18840288 http://dx.doi.org/10.1186/1476-4598-7-77 |
work_keys_str_mv | AT koemilyray aconservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT kodennis aconservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT chencarolyn aconservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT lipsickjosephs aconservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT koemilyray conservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT kodennis conservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT chencarolyn conservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding AT lipsickjosephs conservedacidicpatchinthemybdomainisrequiredforactivationofanendogenoustargetgeneandforchromatinbinding |