# ROLE OF SPECIFIC PROTEINS IN SPERMATOGENESIS

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 1994 · $141,347

## Abstract

Our long term goal is to understand the functional roles and the factors
that regulate the developmental appearance of several novel chromosomal
proteins that are common features of mammalian spermatogenesis.  During the
pachytene stage of meiosis a set of novel variants for all the common
histones except H4 replace to varying degrees their somatic-type
counterparts.  Perhaps the most unusual testis histone variant is H1t,
whose primary structure differs from standard H1 proteins throughout its
length.  Because H1 is the histone responsible for determining the
compaction of nucleosomal DNA, H1t may well impart an unusual structure to
late meiotic and postmeiotic chromosomes.  Later, in spermatids with
condensing nuclei, the histones are replaced by a set of transition
proteins (TP1-4).  The major transition proteins (TP1,2) remain in the
nucleus for approximately 2 days but are then removed, leaving protamines
as the major basic proteins in the mature sperm nucleus.  Presumably the
unusual chromosomal proteins of spermatogenesis play some role ensuring
that meiotic events, genomic imprinting, and chromosome organization in the
sperm nucleus occur appropriately for the male gamete's part in the
development of the embryo.  Information about the functions and regulation
of these proteins could lead to better assessment of some types of male
infertility, the identification of causes of chromosomal abnormalities, of
failures of early development, and a better understanding of chromosomal
structure and gene regulation in general.  Experiments are planned to
dissect the nucleotide sequences that impart specialized expression to the
H1t gene.  Deleted versions of the natural gene and of H1t promoter-
reporter fusions will be tested for appropriate expression in transgenic
mice and somatic cell lines.  In vitro assays of cell free transcription,
gel retardation, and footprinting will identify specific promoter regions
important to regulated expression as well as protein factors that bind to
them.  At least one such factor will be cloned.  To understand the
functional role of H1t, targeted gene disruptions will be made in mouse ES
cells that will be used to produce chimeric mice that can be bred to
generate animals that lack H1t.  The human H1t gene will be isolated and
sequenced to permit its chromosomal localization.  The TP1 promoter region
will be characterized to see if it is responsive to cAMP, as is suggested
by preliminary binding studies with nuclear protein extracts.

## Key facts

- **NIH application ID:** 2196748
- **Project number:** 5R01HD010793-17
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **SAM.gov UEI:** J22LNTMEDP73
- **Principal Investigator:** W STEPHEN KISTLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $141,347
- **Award type:** 5
- **Project period:** 1977-05-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196748

## Citation

> US National Institutes of Health, RePORTER application 2196748, ROLE OF SPECIFIC PROTEINS IN SPERMATOGENESIS (5R01HD010793-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196748. Licensed CC0.

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