PSU Profiles
Keywords
Last Name
Institution

Gregory Yochum

TitleAssistant Professor
InstitutionCollege of Medicine
DepartmentBiochemistry and Molecular Biology
Address500 University Drive Hershey PA 17033
Mailbox: H171
Phone7175312091

 Overview 
 overview
PREFERRED TITLE/ROLE:

Assistant Professor of Biochemistry and Molecular Biology

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

The Huck Institutes of the Life Sciences
The Penn State Hershey Cancer Institute

GRADUATE PROGRAM AFFILIATIONS

Biomedical Sciences: Option in Biochemistry & Molecular Genetics

EDUCATION:

BS Biology, Bucknell University, 1994
Ph.D. Oncological Sciences, University of Utah, 2002
Post-doctoral training, Oregon Health & Sciences University, 2002-2009

NARRATIVE:

The Wnt/ß-catenin signaling pathway is essential for normal intestinal growth and development and inappropriate activation of this pathway is associated with colon cancer. Mutations in components of this signaling pathway lead to high levels of the ß-catenin transcriptional co-activator in the nucleus. Nuclear ß-catenin associates with members of the T-cell factor/ lymphoid enhancer factor (TCF/LEF) family of sequence-specific transcription factors. ß-Catenin/TCF complexes activate target gene expression through recruitment of factors that remodel or modify chromatin structure. Because mutations in Wnt/ß-catenin signaling components are amongst the earliest detected lesions as cells progress from normal colonic epithelial cells to a transformed phenotype, we believe it is essential to identify direct ß-catenin target genes in order to understand the etiology of colon cancer.

My lab uses unbiased and genome-wide methodologies to identify direct ß-catenin binding sites in human colon cancer cell lines. We then use a combination of genetic and molecular biological approaches to determine which putative binding sites confer target gene activation in a Wnt/ß-catenin dependent manner. Using ß-catenin chromatin immunoprecipitation coupled with Serial Analysis of Chromatin Occupancy (SACO), we previously identified a novel Wnt responsive enhancer element (WRE) that resides 1.4 kb downstream of the c-Myc gene. We named this element the MYC 3'WRE. MYC is a proto-oncogene that promotes cell growth and proliferation by controlling expression of genes that regulate metabolism and cell cycle progression. We have shown that the MYC 3' WRE is the principal regulatory element that controls MYC expression in response to Wnt/ß-catenin and mitogen signaling in human colon cancer cells. We are currently determining whether this MYC 3' WRE is required for homeostasis in the mouse intestinal tract. In addition, we are employing ChIP coupled with massively parallel sequencing (ChIP-Seq) to profile ß-catenin binding sites in order to identify those targets whose ß-catenin occupancy changes in response to mitogen signaling.





 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Rennoll SA, Konsavage WM, Yochum GS. Nuclear AXIN2 represses MYC gene expression. Biochem Biophys Res Commun. 2014 Jan 3; 443(1):217-22.
    View in: PubMed
  2. Konsavage WM, Roper JN, Ishmael FT, Yochum GS. The Myc 3' Wnt responsive element regulates neutrophil recruitment after acute colonic injury in mice. Dig Dis Sci. 2013 Oct; 58(10):2858-67.
    View in: PubMed
  3. Konsavage WM, Yochum GS. Intersection of Hippo/YAP and Wnt/ß-catenin signaling pathways. Acta Biochim Biophys Sin (Shanghai). 2013 Feb; 45(2):71-9.
    View in: PubMed
  4. Konsavage WM, Jin G, Yochum GS. The Myc 3' Wnt-responsive element regulates homeostasis and regeneration in the mouse intestinal tract. Mol Cell Biol. 2012 Oct; 32(19):3891-902.
    View in: PubMed
  5. Konsavage WM, Kyler SL, Rennoll SA, Jin G, Yochum GS. Wnt/ß-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem. 2012 Apr 6; 287(15):11730-9.
    View in: PubMed
  6. Wright H, Cohen A, Sönmez K, Yochum G, McWeeney S. Occupancy classification of position weight matrix-inferred transcription factor binding sites. PLoS One. 2011; 6(11):e26160.
    View in: PubMed
  7. Yochum GS. Multiple Wnt/ß-catenin responsive enhancers align with the MYC promoter through long-range chromatin loops. PLoS One. 2011; 6(4):e18966.
    View in: PubMed
  8. Bottomly D, Kyler SL, McWeeney SK, Yochum GS. Identification of {beta}-catenin binding regions in colon cancer cells using ChIP-Seq. Nucleic Acids Res. 2010 Sep; 38(17):5735-45.
    View in: PubMed
  9. Yochum GS, Sherrick CM, Macpartlin M, Goodman RH. A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5' and 3' Wnt responsive enhancers. Proc Natl Acad Sci U S A. 2010 Jan 5; 107(1):145-50.
    View in: PubMed
  10. McWeeney SK, Pemberton LC, Loriaux MM, Vartanian K, Willis SG, Yochum G, Wilmot B, Turpaz Y, Pillai R, Druker BJ, Snead JL, MacPartlin M, O'Brien SG, Melo JV, Lange T, Harrington CA, Deininger MW. A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib. Blood. 2010 Jan 14; 115(2):315-25.
    View in: PubMed
  11. Yochum GS, Cleland R, Goodman RH. A genome-wide screen for beta-catenin binding sites identifies a downstream enhancer element that controls c-Myc gene expression. Mol Cell Biol. 2008 Dec; 28(24):7368-79.
    View in: PubMed
  12. Yochum GS, Rajaraman V, Cleland R, McWeeney S. Localization of TFIIB binding regions using serial analysis of chromatin occupancy. BMC Mol Biol. 2007; 8:102.
    View in: PubMed
  13. Otto SJ, McCorkle SR, Hover J, Conaco C, Han JJ, Impey S, Yochum GS, Dunn JJ, Goodman RH, Mandel G. A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions. J Neurosci. 2007 Jun 20; 27(25):6729-39.
    View in: PubMed
  14. Yochum GS, McWeeney S, Rajaraman V, Cleland R, Peters S, Goodman RH. Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells. Proc Natl Acad Sci U S A. 2007 Feb 27; 104(9):3324-9.
    View in: PubMed
  15. Yochum GS, Cleland R, McWeeney S, Goodman RH. An antisense transcript induced by Wnt/beta-catenin signaling decreases E2F4. J Biol Chem. 2007 Jan 12; 282(2):871-8.
    View in: PubMed
  16. Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, McWeeney S, Dunn JJ, Mandel G, Goodman RH. Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell. 2004 Dec 29; 119(7):1041-54.
    View in: PubMed
  17. Cha-Molstad H, Keller DM, Yochum GS, Impey S, Goodman RH. Cell-type-specific binding of the transcription factor CREB to the cAMP-response element. Proc Natl Acad Sci U S A. 2004 Sep 14; 101(37):13572-7.
    View in: PubMed
  18. Yochum GS, Ayer DE. Role for the mortality factors MORF4, MRGX, and MRG15 in transcriptional repression via associations with Pf1, mSin3A, and Transducin-Like Enhancer of Split. Mol Cell Biol. 2002 Nov; 22(22):7868-76.
    View in: PubMed
  19. Yochum GS, Ayer DE. Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex. Mol Cell Biol. 2001 Jul; 21(13):4110-8.
    View in: PubMed
  20. Brubaker K, Cowley SM, Huang K, Loo L, Yochum GS, Ayer DE, Eisenman RN, Radhakrishnan I. Solution structure of the interacting domains of the Mad-Sin3 complex: implications for recruitment of a chromatin-modifying complex. Cell. 2000 Nov 10; 103(4):655-65.
    View in: PubMed
  21. Adler AJ, Huang CT, Yochum GS, Marsh DW, Pardoll DM. In vivo CD4+ T cell tolerance induction versus priming is independent of the rate and number of cell divisions. J Immunol. 2000 Jan 15; 164(2):649-55.
    View in: PubMed
  22. Laherty CD, Billin AN, Lavinsky RM, Yochum GS, Bush AC, Sun JM, Mullen TM, Davie JR, Rose DW, Glass CK, Rosenfeld MG, Ayer DE, Eisenman RN. SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors. Mol Cell. 1998 Jul; 2(1):33-42.
    View in: PubMed
  23. Adler AJ, Marsh DW, Yochum GS, Guzzo JL, Nigam A, Nelson WG, Pardoll DM. CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells. J Exp Med. 1998 May 18; 187(10):1555-64.
    View in: PubMed
Yochum's Networks
Click the "See All" links for more information and interactive visualizations!
Concepts
_
Co-Authors
_
Similar People
_
Same Department
Physical Neighbors
_