Mechanism of Histone Variant Swithing
{'Code': '08070100', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'DeLill Nasser'}
The multigene histone family displays a number of fascinating                   properties; cell-cycle regulation, transcriptional and post-                    transcriptional control, coordinate regulation and                              differential gene expression of individual members within a                     family.  The objectives of this proposal concern                                determination of the level of regulation of partially                           replication-dependent (PRD) to fully replication-dependent                      (FRD) histone gene switching during differentiation of murine                   erythroleukemia (MEL) cells.  We will begin to identify the                     signals involved in this regulation.  We propose several                        approaches to determine the extent to which transcriptional                     and post-transcriptional regulation are involved in histone                     gene switching.  These approaches include: 1) Testing of PRD                    and FRD genes in DNA-dependent transcription extracts for                       differential changes in transcription efficiency.  2)                           Establishment of gene constructs which are regulated, after                     transformation, in a PRD or FRD manner.  3) Determination of                    the changes in transcription rates of individual histone                        genes during differentiation, using in vitro nuclear                            transcription.  4) Measurement of the half-life of different                    histone mRNAs during differentiation.  We will then extend                      these approaches to map the signals involved in this                            regulation.                                                                                                                                                     The histones are known to be essential to the structural                        integrity of chromatin but their role, if any, in the                           regulation of gene expression is obscure.  A better                             understanding of the histone gene switching which occurs                        during differentiation of the murine erythroleukemia cells                      may give some insight into the effect upon gene expression if                   such exists.
{'FirstName': 'Donald', 'LastName': 'Sittman', 'EmailAddress': 'dsittman@biochem.umsmed.edu', 'StartDate': '08/01/1989', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of Mississippi Medical Center', 'CityName': 'Jackson', 'ZipCode': '392164505', 'PhoneNumber': '6018155000', 'StreetAddress': '2500 North State Street', 'CountryName': 'United States', 'StateName': 'Mississippi', 'StateCode': 'MS'}
{'Code': '1116', 'Text': 'EUKARYOTIC GENETICS'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8818958.xml'}