Recently microarray technoloy has been implemented for measurements such as genome wide transcription patterns, and chromation immunoprecipitation analysis using genomic fragment arrays has been shown to be feasible for mammalian cells. Large scale gene knockdown experiments are also now achievable for analysis of gene function in cells from multizoates. Multipotential mesenchymal cells have been identified that can be propagated indefinitely amd differentiate within weeks into any one of a number of different cell lineages, in a manner controlled by the culture conditions. In addition to sequence specific DNA binding proteins, gene expression can be modified by the state of DNA methylation and the types and positions of modified residues in the core histones of nucleosomes. Further groups of proteins have been identified genetically and biochemically that function to stabilize gene activity or silence and interact with or participate in chromatin modification. The ability to rapidly undergo commitment to any of a number of cell lineages may be coupled to either limitations in the mechanisms for maintenance of gene activation or silencing or efficient functioning of mechanisms to reverse silenced and activated states of genes. Application of the new generation of genomic techniques could give fundamental insight into the mechanisms of multipotentiality and lineage choice and potential guide experimentation towards the development of regenerative medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG023111-03
Application #
7084432
Study Section
Genome Study Section (GNM)
Program Officer
Williams, John
Project Start
2004-09-01
Project End
2009-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$583,655
Indirect Cost
Name
Yale University
Department
Genetics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Ye, Zhi-jia; Gulcicek, Erol; Stone, Kathryn et al. (2011) Complex interactions in EML cell stimulation by stem cell factor and IL-3. Proc Natl Acad Sci U S A 108:4882-7
Liu, Zhong; Hu, Zhe; Pan, Xinghua et al. (2011) Germline competency of parthenogenetic embryonic stem cells from immature oocytes of adult mouse ovary. Hum Mol Genet 20:1339-52
Karmakar, Subhradip; Mahajan, Milind C; Schulz, Vincent et al. (2010) A multiprotein complex necessary for both transcription and DNA replication at the ýý-globin locus. EMBO J 29:3260-71
Mahajan, Milind C; Karmakar, Subhradip; Newburger, Peter E et al. (2009) Dynamics of alpha-globin locus chromatin structure and gene expression during erythroid differentiation of human CD34(+) cells in culture. Exp Hematol 37:1143-1156.e3
Pan, Xinghua; Urban, Alexander Eckehart; Palejev, Dean et al. (2008) A procedure for highly specific, sensitive, and unbiased whole-genome amplification. Proc Natl Acad Sci U S A 105:15499-504
Ye, Zhi-jia; Kluger, Yuval; Lian, Zheng et al. (2005) Two types of precursor cells in a multipotential hematopoietic cell line. Proc Natl Acad Sci U S A 102:18461-6