Role of histone variants in regulating chromatin structure and function
Histone variants, chromatin, macroH2A, inactive X chromosome, gene regulation.
Description of Research
We are studying macroH2A core histone variants. These proteins are three times the size of conventional core histones, and have a hybrid structure consisting of a large nonhistone region and a region that closely resembles a conventional histone H2A. There are three macroH2A variants and two macroH2A genes. MacroH2A proteins are preferentially concentrated on the transcriptionally inactive X chromosome of female mammals and certain other domains of heterochromatin, indicating that macroH2As are involved in establishing or maintaining specific domains of transcriptionally silent chromatin. In order to test and expand on this theory, we are examining the effects of macroH2A knockout mutations on gene expression in vivo. We are also examining the distribution of macroH2A1 nucleosomes in order to identify regions of chromatin that are being directly affected by macroH2A.
Rotation Projects for 2006-2007
Please see Dr Pehrson.
Lakshmi N. Changolkar, M.S., Research Specialist
Geetika Singh, M.S., Research Specialist
Adrian N. Leu, B.S. Research Specialist
Bernstein E, Muratore T, Diaz R, Chow J, Changolkar LN, Shabinowitz J, Heard E, Pehrson JR, Hunt DF, and Allis CD: A phosphorylated sub-population of the histone variant macroH2A is enriched during mitosis and excluded from the inactive X chromosome. Academic Science USA 105: 1533-1538, 2008.
Changolkar LN, Singh G, and Pehrson JR.: MacroH2A1-mediated silencing of endogenous murine leukemia viruses. Molecular & Cellular Biology 28: 2059-2065, 2008.
Changolkar, Lakshmi N. Costanzi, Carl. Leu, N Adrian. Chen, Dannee. McLaughlin, K John. Pehrson, John R.: Developmental changes in histone macroH2A1-mediated gene regulation. Molecular & Cellular Biology 27(7): 2758-64, Apr 2007.
Zhang, Rugang. Liu, Song-tao. Chen, Wei. Bonner, Michael. Pehrson, John. Yen, Timothy J. Adams, Peter D.: HP1 proteins are essential for a dynamic nuclear response that rescues the function of perturbed heterochromatin in primary human cells. Molecular & Cellular Biology 27(3): 949-62, Feb 2007.
Changolkar, Lakshmi N. Pehrson, John R.: macroH2A1 histone variants are depleted on active genes but concentrated on the inactive X chromosome. Molecular & Cellular Biology 26(12): 4410-20, Jun 2006.
Chakravarthy, Srinivas. Gundimella, Sampath Kumar Y. Caron, Cecile. Perche, Pierre-Yves. Pehrson, John R. Khochbin, Saadi. Luger, Karolin.: Structural characterization of the histone variant macroH2A. Molecular & Cellular Biology 25(17): 7616-24, Sep 2005.
Zhang, Rugang. Poustovoitov, Maxim V. Ye, Xiaofen. Santos, Hidelita A. Chen, Wei. Daganzo, Sally M. Erzberger, Jan P. Serebriiskii, Ilya G. Canutescu, Adrian A. Dunbrack, Roland L. Pehrson, John R. Berger, James M. Kaufman, Paul D. Adams, Peter D.: Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Developmental Cell 8(1): 19-30, Jan 2005.
Grigoryev, Sergei A. Nikitina, Tatiana. Pehrson, John R. Singh, Prim B. Woodcock, Christopher L.: Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence. Journal of Cell Science 117(Pt 25): 6153-62, Dec 1 2004.
Hoyer-Fender, Sigrid. Czirr, Eva. Radde, Rebecca. Turner, James M A. Mahadevaiah, Shantha K. Pehrson, John R. Burgoyne, Paul S.: Localisation of histone macroH2A1.2 to the XY-body is not a response to the presence of asynapsed chromosome axes. Journal of Cell Science 117(Pt 2): 189-98, Jan 15 2004.
Changolkar, Lakshmi N. Pehrson, John R.: Histone macroH2A purification and nucleosome reconstitution. Methods in Enzymology 375: 228-38, 2004.
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Last updated: 04/29/2015
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