Regulation of Gene Expression at the Level of               Transcriptional Elongation
{'Code': '08070100', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'DeLill Nasser', 'PO_EMAI': None, 'PO_PHON': None}
A series of experiments are proposed to continue our                            investigation of the block to elongation of transcription of                    the human c-myce gene, which was observed originally by                         nuclear runoff transcription in the HL60 cell line.                             Preliminary results are presented indicating that the block                     to elongation as assayed by runoff transcription is also                        observed when the human c-myce gene is transcribed in the                       context o> the xenopus oocyte.  In addition, prematurely                        terminated and sÕcble RNA's with 3' terminal mapping near the                   end of exon 1 are initiated from tie two major human c-myc                      promoters after injection of human gene into the oocyte.                        Deletion analyses reveal that sequences sufficient to control                   the observed premature termination are located within a 95                      base pair region upstream of a Pvu II site 40 bases 5' of the                   saxon 1/intron 1 boundary.  Termination activity in these                       sequences is orientation dependent and functions downstream                     of the HSV-Tk, but not the adenovirus 2 major late promoter.                    Interestingly, these sequences are either eliminated or                         mutated in Burkitt lymphoma, and the block to elongation is                     alleviated in these cells.  A series of experiments are                         proposed that will: 1.) provide independent verification of                     the in vivo distribution of RNA polymerase II in the c-myc                      gene in human cells; 2.) define sequences in cis necessary                      and sufficient for premature termination of thm human c-myc                     gene injected into xmoopus oocytes and the block to                             elongation of transcription in the luman c-myc gene in                          mammalian cells; 3.) determine the basis of read through                        transcription of c-myc in Burkitt lymphoma cells; and 4.)                       identify factors which interact with the sequences necessary                    for the block to elongation and, through in vitro                               transcription assays, determine their contribution to                           elongation.                                                                                                                                                     The regulation of transcription of eukaryotic genes is a                        central control mechanism in differential gene expression.                      While many investigators are studying the mechanisms                            involved with the initiation of transcription, few are                          focusing on the equally important levels of transcript                          elongation and terminetion.  The results of this                                investigation should provide information leading to$a better                    understanding of this pro>ess in eukaryotic cells.
{'FirstName': 'Mark', 'LastName': 'Groudine', 'PI_MID_INIT': 'T', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Mark T Groudine', 'EmailAddress': None, 'NSF_ID': '000209601', 'StartDate': '07/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Fred Hutchinson Cancer Research Center', 'CityName': 'SEATTLE', 'ZipCode': '981094433', 'PhoneNumber': '2066674868', 'StreetAddress': '1100 FAIRVIEW AVE N J6-300', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Washington', 'StateCode': 'WA', 'CONGRESSDISTRICT': '07', 'CONGRESS_DISTRICT_ORG': 'WA07', 'ORG_UEI_NUM': 'HMSNCM57QNR5', 'ORG_LGL_BUS_NAME': 'FRED HUTCHINSON CANCER RESEARCH CENTER', 'ORG_PRNT_UEI_NUM': 'HMSNCM57QNR5'}
{'Name': None, 'CityName': None, 'StateCode': None, 'ZipCode': None, 'StreetAddress': None, 'CountryCode': None, 'CountryName': None, 'StateName': None, 'CountryFlag': None, 'CONGRESSDISTRICT': None, 'CONGRESS_DISTRICT_PERF': '""'}
{'Code': '1116', 'Text': 'EUKARYOTIC GENETICS'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8802490.xml'}