The CSRP2BP histone acetyltransferase drives smooth muscle gene expression
The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle g...
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| Published in | Nucleic acids research Vol. 45; no. 6; pp. 3046 - 3058 |
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| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Oxford University Press
07.04.2017
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| Abstract | The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression. |
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| AbstractList | The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression. The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression. The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression.The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression. |
| Author | Sun, Fei Huang, Yuanhua Jiang, Xinxing Li, Qi Yu, Wei Li, Ankang Liang, Chao Wu, Bangyong Wang, Jun Weiskirchen, Ralf Schwartz, Robert J. Long, Ping Ma, Yanlin Wei, Yanxing Wei, Yunjian Grötzinger, Joachim Mercola, Mark Yu, Yanhong |
| AuthorAffiliation | 8 Stem Cell and Regeneration Program, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA 1 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China 9 Texas Heart Institute, Houston, TX 77030, USA 6 Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, 24098 Kiel, Germany 3 The Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA 5 Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, University Hospital Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany 4 Graduate Program in Cardiovascular Sciences, Baylor College of Medicine, Houston, TX 77030, USA 2 Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The Key Laboratory of Tropical Diseases and Translational Medicine of The Ministry of Education, Affiliated Hospital of |
| AuthorAffiliation_xml | – name: 2 Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The Key Laboratory of Tropical Diseases and Translational Medicine of The Ministry of Education, Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan 570102, China – name: 5 Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, University Hospital Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany – name: 6 Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, 24098 Kiel, Germany – name: 9 Texas Heart Institute, Houston, TX 77030, USA – name: 7 Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA – name: 1 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China – name: 8 Stem Cell and Regeneration Program, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA – name: 4 Graduate Program in Cardiovascular Sciences, Baylor College of Medicine, Houston, TX 77030, USA – name: 3 The Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA |
| Author_xml | – sequence: 1 givenname: Yanlin surname: Ma fullname: Ma, Yanlin – sequence: 2 givenname: Qi surname: Li fullname: Li, Qi – sequence: 3 givenname: Ankang surname: Li fullname: Li, Ankang – sequence: 4 givenname: Yunjian surname: Wei fullname: Wei, Yunjian – sequence: 5 givenname: Ping surname: Long fullname: Long, Ping – sequence: 6 givenname: Xinxing surname: Jiang fullname: Jiang, Xinxing – sequence: 7 givenname: Fei surname: Sun fullname: Sun, Fei – sequence: 8 givenname: Ralf surname: Weiskirchen fullname: Weiskirchen, Ralf – sequence: 9 givenname: Bangyong surname: Wu fullname: Wu, Bangyong – sequence: 10 givenname: Chao surname: Liang fullname: Liang, Chao – sequence: 11 givenname: Joachim surname: Grötzinger fullname: Grötzinger, Joachim – sequence: 12 givenname: Yanxing surname: Wei fullname: Wei, Yanxing – sequence: 13 givenname: Wei surname: Yu fullname: Yu, Wei – sequence: 14 givenname: Mark surname: Mercola fullname: Mercola, Mark – sequence: 15 givenname: Yuanhua surname: Huang fullname: Huang, Yuanhua – sequence: 16 givenname: Jun surname: Wang fullname: Wang, Jun – sequence: 17 givenname: Yanhong surname: Yu fullname: Yu, Yanhong – sequence: 18 givenname: Robert J. surname: Schwartz fullname: Schwartz, Robert J. |
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| Snippet | The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not... |
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| SubjectTerms | Acetylation Animals Cell Line Cell Nucleus - enzymology Cells, Cultured Chromatin - enzymology Gene Expression Gene Expression Regulation Gene regulation, Chromatin and Epigenetics Histone Acetyltransferases - metabolism Histones - metabolism Humans Mice Myocytes, Smooth Muscle - enzymology Myocytes, Smooth Muscle - metabolism Nuclear Proteins - metabolism Promoter Regions, Genetic Rats Trans-Activators - metabolism Transcription Factors - metabolism |
| Title | The CSRP2BP histone acetyltransferase drives smooth muscle gene expression |
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