The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells
The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase (HAT) complex acetylates histone H4 at lysine K5, K8, and K16. This complex shares several subunits with other epigenetic regulatory enzymes, which highlights the complexity of its intracellular...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/3801 |
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| author | Hongsen Liu Tao Wei Lin Sun Tingting Wu Fuqiang Li Jianlei Zhao Jinmeng Chu Fei Wang Yong Cai Jingji Jin |
| author_facet | Hongsen Liu Tao Wei Lin Sun Tingting Wu Fuqiang Li Jianlei Zhao Jinmeng Chu Fei Wang Yong Cai Jingji Jin |
| author_sort | Hongsen Liu |
| collection | DOAJ |
| description | The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase (HAT) complex acetylates histone H4 at lysine K5, K8, and K16. This complex shares several subunits with other epigenetic regulatory enzymes, which highlights the complexity of its intracellular function. However, the effect of the NSL HAT complex on the genome and target genes in human cells is still unclear. By using a CRISPR/Cas9-mediated NSL3-knockout 293T cell line and chromatin immunoprecipitation-sequencing (ChIP-Seq) approaches, we identified more than 100 genes as NSL HAT transcriptional targets, including several transcription factors, such as <i>Yin Yang 1</i> (<i>YY1</i>) which are mainly involved in cell proliferation, biological adhesion, and metabolic processes. We found here that the ChIP-Seq peaks of MOF and NSL3 co-localized with H4K16ac, H3K4me2, and H3K4me3 at the transcriptional start site of YY1. In addition, both the mRNA and protein expression levels of YY1 were regulated by silencing or overexpressing NSL HAT. Interestingly, the expression levels of cell division cycle 6, a downstream target gene of YY1, were regulated by MOF or NSL3. In addition, the suppressed clonogenic ability of HepG2 cells caused by siNSL3 was reversed by overexpressing YY1, suggesting the involvement of YY1 in NSL HAT functioning. Additionally, de novo motif analysis of MOF and NSL3 targets indicated that the NSL HAT complex may recognize the specific DNA-binding sites in the promoter region of target genes in order to regulate their transcription. |
| first_indexed | 2024-03-09T11:45:51Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:45:51Z |
| publishDate | 2022-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c6896368c42044c29ea55bcfcf65c8572023-11-30T23:22:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237380110.3390/ijms23073801The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human CellsHongsen Liu0Tao Wei1Lin Sun2Tingting Wu3Fuqiang Li4Jianlei Zhao5Jinmeng Chu6Fei Wang7Yong Cai8Jingji Jin9School of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaThe human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase (HAT) complex acetylates histone H4 at lysine K5, K8, and K16. This complex shares several subunits with other epigenetic regulatory enzymes, which highlights the complexity of its intracellular function. However, the effect of the NSL HAT complex on the genome and target genes in human cells is still unclear. By using a CRISPR/Cas9-mediated NSL3-knockout 293T cell line and chromatin immunoprecipitation-sequencing (ChIP-Seq) approaches, we identified more than 100 genes as NSL HAT transcriptional targets, including several transcription factors, such as <i>Yin Yang 1</i> (<i>YY1</i>) which are mainly involved in cell proliferation, biological adhesion, and metabolic processes. We found here that the ChIP-Seq peaks of MOF and NSL3 co-localized with H4K16ac, H3K4me2, and H3K4me3 at the transcriptional start site of YY1. In addition, both the mRNA and protein expression levels of YY1 were regulated by silencing or overexpressing NSL HAT. Interestingly, the expression levels of cell division cycle 6, a downstream target gene of YY1, were regulated by MOF or NSL3. In addition, the suppressed clonogenic ability of HepG2 cells caused by siNSL3 was reversed by overexpressing YY1, suggesting the involvement of YY1 in NSL HAT functioning. Additionally, de novo motif analysis of MOF and NSL3 targets indicated that the NSL HAT complex may recognize the specific DNA-binding sites in the promoter region of target genes in order to regulate their transcription.https://www.mdpi.com/1422-0067/23/7/3801histone acetyltransferasegene transcriptioncell proliferationtranscription factorYin Yang 1epigenetics |
| spellingShingle | Hongsen Liu Tao Wei Lin Sun Tingting Wu Fuqiang Li Jianlei Zhao Jinmeng Chu Fei Wang Yong Cai Jingji Jin The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells International Journal of Molecular Sciences histone acetyltransferase gene transcription cell proliferation transcription factor Yin Yang 1 epigenetics |
| title | The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells |
| title_full | The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells |
| title_fullStr | The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells |
| title_full_unstemmed | The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells |
| title_short | The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells |
| title_sort | non specific lethal nsl histone acetyltransferase complex transcriptionally regulates yin yang 1 mediated cell proliferation in human cells |
| topic | histone acetyltransferase gene transcription cell proliferation transcription factor Yin Yang 1 epigenetics |
| url | https://www.mdpi.com/1422-0067/23/7/3801 |
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