TY - JOUR
T1 - Reprogramming the male gamete genome
T2 - A window to successful gene therapy
AU - Krawetz, S. A.
AU - Kramer, J. A.
AU - McCarrey, J. R.
N1 - Funding Information:
Support from the Wayne State University FMRE and Research Faculty award to S.A.K. are gratefully acknowledged. J.A.K. was supported in part by a grant from the Lalor Foundation. This work was supported in part by NIH grant HD36512 to S.A.K. and HD23126 to J.R.M. The authors wish to thank Ms S. Wykes for the artist's rendering of the various cells from the spermatogenic pathway.
PY - 1999/6/24
Y1 - 1999/6/24
N2 - Hematopoiesis and spermatogenesis both initiate from a stem cell capable of renewal and differentiation. Each pathway reflects the expression of unique combinations of facultative, i.e. tissue-specific and constitutive, i.e. housekeeping, genes in each cell type. In spermatogenesis, as in hematopoiesis, commitment is mediated by the mechanism of potentiation whereby specific chromatin domains are selectively opened along each chromosome. Within each open chromatin domain, a unique battery of gene(s) is availed to tissue-specific and ubiquitous transacting factors that are necessary to initiate transcription. In the absence of an open domain, trans-factor access is denied, and the initiation of transcription cannot proceed. Cell-fate is thus ultimately defined by the unique series of open-potentiated cell-specific chromatin domains. Defining the mechanism that opens chromatin domains is fundamental in understanding how differentiation from stem cells is controlled and whether cell-fate can be modified. A recent examination of the mammalian spermatogenic pathway [ Kramer, J.A., McCarrey, J.M, Djakiew, D., Krawetz, S.A., 1998. Differentiation: the selective potentiation of chromatin domains. Development 125, 4749-4755] supports the view that cell fate is mediated by global changes in chromatin conformation. This stride underscores the possibility of moderating differentiation through chromatin conformation. It is likely that gene therapeutics capable of selectively potentiating individual genic domains in populations of differentiating and/or replicating cells that modify cellular phenotype will be developed in the next millennium. (C) 1999 Elsevier Science B.V. All rights reserved.
AB - Hematopoiesis and spermatogenesis both initiate from a stem cell capable of renewal and differentiation. Each pathway reflects the expression of unique combinations of facultative, i.e. tissue-specific and constitutive, i.e. housekeeping, genes in each cell type. In spermatogenesis, as in hematopoiesis, commitment is mediated by the mechanism of potentiation whereby specific chromatin domains are selectively opened along each chromosome. Within each open chromatin domain, a unique battery of gene(s) is availed to tissue-specific and ubiquitous transacting factors that are necessary to initiate transcription. In the absence of an open domain, trans-factor access is denied, and the initiation of transcription cannot proceed. Cell-fate is thus ultimately defined by the unique series of open-potentiated cell-specific chromatin domains. Defining the mechanism that opens chromatin domains is fundamental in understanding how differentiation from stem cells is controlled and whether cell-fate can be modified. A recent examination of the mammalian spermatogenic pathway [ Kramer, J.A., McCarrey, J.M, Djakiew, D., Krawetz, S.A., 1998. Differentiation: the selective potentiation of chromatin domains. Development 125, 4749-4755] supports the view that cell fate is mediated by global changes in chromatin conformation. This stride underscores the possibility of moderating differentiation through chromatin conformation. It is likely that gene therapeutics capable of selectively potentiating individual genic domains in populations of differentiating and/or replicating cells that modify cellular phenotype will be developed in the next millennium. (C) 1999 Elsevier Science B.V. All rights reserved.
KW - Cell fate
KW - Commitment
KW - Determination
KW - Gene therapy
KW - Potentiation
KW - Stem cell
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U2 - 10.1016/S0378-1119(99)00147-X
DO - 10.1016/S0378-1119(99)00147-X
M3 - Review article
C2 - 10393233
AN - SCOPUS:0032967471
SN - 0378-1119
VL - 234
SP - 1
EP - 9
JO - Gene
JF - Gene
IS - 1
ER -