Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region - PubMed (original) (raw)
Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region
M A Bender et al. Mol Cell. 2000 Feb.
Free article
Abstract
We have generated mice with a targeted deletion of the beta-globin locus control region (LCR). Mice homozygous for the deletion die early in embryogenesis but can be rescued with a YAC containing the human beta-globin locus. After germline passage, deletion of the LCR leads to a severe reduction in expression of all mouse beta-like globin genes, but no alteration in the developmental specificity of expression. Furthermore, a DNase I-sensitive "open" chromatin conformation of the locus is established and maintained. Thus, the dominant role of the LCR in the native locus is to confer high-level transcription, and elements elsewhere in the locus are sufficient to establish and maintain an open conformation and to confer developmentally regulated globin gene expression.
Similar articles
- Hypersensitive site 2 specifies a unique function within the human beta-globin locus control region to stimulate globin gene transcription.
Bungert J, Tanimoto K, Patel S, Liu Q, Fear M, Engel JD. Bungert J, et al. Mol Cell Biol. 1999 Apr;19(4):3062-72. doi: 10.1128/MCB.19.4.3062. Mol Cell Biol. 1999. PMID: 10082573 Free PMC article. - Individual LCR hypersensitive sites cooperate to generate an open chromatin domain spanning the human beta-globin locus.
Li G, Lim KC, Engel JD, Bungert J. Li G, et al. Genes Cells. 1998 Jul;3(7):415-29. doi: 10.1046/j.1365-2443.1998.00200.x. Genes Cells. 1998. PMID: 9753424 - beta-YAC transgenic mice for studying LCR function.
Peterson KR, Navas PA, Stamatoyannopoulos G. Peterson KR, et al. Ann N Y Acad Sci. 1998 Jun 30;850:28-37. doi: 10.1111/j.1749-6632.1998.tb10459.x. Ann N Y Acad Sci. 1998. PMID: 9668524 Review. - Deletion of the core region of 5' HS2 of the mouse beta-globin locus control region reveals a distinct effect in comparison with human beta-globin transgenes.
Hu X, Bulger M, Bender MA, Fields J, Groudine M, Fiering S. Hu X, et al. Blood. 2006 Jan 15;107(2):821-6. doi: 10.1182/blood-2005-06-2308. Epub 2005 Sep 27. Blood. 2006. PMID: 16189270 Free PMC article. - Looping, linking, and chromatin activity: new insights into beta-globin locus regulation.
Engel JD, Tanimoto K. Engel JD, et al. Cell. 2000 Mar 3;100(5):499-502. doi: 10.1016/s0092-8674(00)80686-8. Cell. 2000. PMID: 10721987 Review. No abstract available.
Cited by
- Genomic context sensitizes regulatory elements to genetic disruption.
Ordoñez R, Zhang W, Ellis G, Zhu Y, Ashe HJ, Ribeiro-Dos-Santos AM, Brosh R, Huang E, Hogan MS, Boeke JD, Maurano MT. Ordoñez R, et al. Mol Cell. 2024 May 16;84(10):1842-1854.e7. doi: 10.1016/j.molcel.2024.04.013. Mol Cell. 2024. PMID: 38759624 - Cell fate decision in erythropoiesis: Insights from multiomics studies.
Tur S, Palii CG, Brand M. Tur S, et al. Exp Hematol. 2024 Mar;131:104167. doi: 10.1016/j.exphem.2024.104167. Epub 2024 Jan 21. Exp Hematol. 2024. PMID: 38262486 Review. - Super-enhancers include classical enhancers and facilitators to fully activate gene expression.
Blayney JW, Francis H, Rampasekova A, Camellato B, Mitchell L, Stolper R, Cornell L, Babbs C, Boeke JD, Higgs DR, Kassouf M. Blayney JW, et al. Cell. 2023 Dec 21;186(26):5826-5839.e18. doi: 10.1016/j.cell.2023.11.030. Epub 2023 Dec 14. Cell. 2023. PMID: 38101409 Free PMC article. - Genomic context sensitizes regulatory elements to genetic disruption.
Ordoñez R, Zhang W, Ellis G, Zhu Y, Ashe HJ, Ribeiro-Dos-Santos AM, Brosh R, Huang E, Hogan MS, Boeke JD, Maurano MT. Ordoñez R, et al. bioRxiv [Preprint]. 2024 Mar 12:2023.07.02.547201. doi: 10.1101/2023.07.02.547201. bioRxiv. 2024. PMID: 37781588 Free PMC article. Updated. Preprint. - Rho enhancers play unexpectedly minor roles in Rhodopsin transcription and rod cell integrity.
Sun C, Ruzycki PA, Chen S. Sun C, et al. Sci Rep. 2023 Aug 9;13(1):12899. doi: 10.1038/s41598-023-39979-6. Sci Rep. 2023. PMID: 37558693 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases