Cell Molecular Final
Intracellular Receptors for Steroid Hormones
- Common nonpolar, lipid-soluble structure - Can cross the plasma membrane - Binding of the hormone to the receptor causes the complex to shift from the cytoplasm to the nucleus - Act as regulators of gene expression
10%
About ___ of the genes in the human genome encode transcription factors, emphasizing the importance of these gene-specific transcription factors
2000
About ___ transcription factors are encoded in the human genome. They contain many distinct types of DNA-binding domains
B Recognition Element
BRE cis-regulatory element that is found immediately upstream of the TATA box, and consists of 7 nucleotides
Lipid-Soluble Steroid Hormones
Bind to receptors inside the cell Trigger a change in the cell's activity directly
CREB-Binding Protein
CBP a protein that in humans is encoded by the CREBBP gene and carries out its function by activating transcription, where interaction with transcription factors is managed by one or more CREB domains
cAMP Response Element
CRE
cAMP Response Element-Binding Protein
CREB a cellular transcription factor that binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes
Carboxy-Terminal Domain
CTD The C-terminus of Pol II is This domain of RNA polymerase II typically consists of up to 52 repeats of the sequence Y-S-P-T-S-P-S. This domain is involved in the initiation of transcription, capping of the RNA transcript, and attachment to the spliceosome for RNA splicing.
TATA Box
Core Promoter Element a DNA sequence that indicates where a genetic sequence can be read and decoded a type of promoter sequence, which specifies to other molecules where transcription begins.
Downstream Core Element
DCE a transcription core promoter sequence that is within the transcribed portion of a gene. CTTC...CTGT...AGC
Leucine Zipper, Helix-Loop-Helix
DNA-binding domains are formed by dimerization of two polypeptide chains
Downstream Core Promoter Element
DPE a core promoter element located precisely +28 to +32 nts relative to the A+1 nt
Spoke-Ring Assembly
Eight spokes are connected to rings at the nuclear and cytoplasmic surfaces surrounds a central channel Protein filaments extend from the rings, forming a basketlike structure on the nuclear side
Transcription, Translation, Post-Translation
Eukaryotes can control gene expression at levels of...
Chromatin Remodeling, RNA processing to produce a mature mRNA, Regulation of mRNA life span or stability
Eukaryotes have three levels of control:
Hutchinson-Gilford Progeria Syndrome
HGPS A premature aging disease caused by LMNA gene mutations typically appear normal at birth, but show growth retardation before the age of 2 years Further manifestations include loss of hair, lipodystrophy, sclerodermatous skin, osteolysis, and progressive atherosclerosis leading to death at an average age of 13 years due to myocardial infarcts and strokes Most patients carry the 1824C>T mutation (G608G), which activates a cryptic splice site resulting in the expression of LA with 50 amino acids deleted near its C terminus (LAΔ50/progerin) As a result, LAΔ50/progerin remains permanently farnesylated , and its accumulation in patients' cells is correlated with the loss of heterochromatin and changes in histone methylation
Retinoic Acid Teratogenesis
Hox gene expression borders move into more anterior regions
Initiator Element
Inr a core promoter that is similar in function to the TATA box has the consensus sequence YYANWYY
Hormone-Receptor Complex
Is transported to the nucleus where it alters gene expression
Lamin B Receptor
LBR
Motif Ten Element
MTE downstream core promoter element located precisely at positions +18 to +27 relative to A+1 in the initiator (Inr) element consensus sequence is [5'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-3']
Negative Elongation Factor
NELF negatively impacts transcription by Pol II by pausing about 20-60 nucleotides downstream from the transcription start site
Nuclear Export Signals
NES amino acid sequences that target proteins for exports recognized by exportins
Neonatal Progeroid Syndrome
NPS affects only a handful of people worldwide The most telling features of the condition are an aged appearance and extreme thinness
Elongation
Only one of the unwound DNA strands acts as a template for RNA synthesis.
Positive Transcription Elongation Factor B
P-TEFb a cyclin dependent kinase that can phosphorylate DSIF and NELF as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs
B
Problem: Deacetylation of histones has which of the following effects? A. Coiling of the histone structure, allowing it to be accessed by transcriptional machinery B. Coiling of the histone structure, preventing it from being accessed by transcriptional machinery C. Uncoiling of histone structure, preventing it from being accessed by transcriptional machinery D. Uncoiling of histone structure, allowing it to be accessed by transcriptional machinery
Retinoic Acid Receptor Response Element
RARE found in Hox elements in the DNA before paralogue 1 controls expression of many genes in the Hox Complex
Initiation
RNA polymerase binds to DNA at a specific sequence of nucleotides called the promoter. RNA polymerase then unwinds DNA at the beginning of the gene The TATA-binding protein (TBP, a subunit of TFIID), TBPL1, or TBPL2 can bind the promoter or TATA box. TBP is always involved and is forced to bind without sequence specificity.
Termination
RNA polymerase continues to elongate until it reaches the terminator, Transcription stops and mRNA polymerase and the new mRNA transcript are released from DNA.
Ribonucleoprotein Complexes
RNPs RNAs that are transported to the cytoplasm
Transcription Activation Domain
TAD a transcription factor scaffold domain which contains binding sites for other proteins such as transcription coregulators
Topologically Associated Domains
TADs Genomes divided into discrete chromosomal domains
TATA-Binding Protein Associated Factor
TAF forms part of Transcription factor II D (TFIID) and the TATA-binding protein (TBP). They mediate transcription of DNA to RNA by RNA polymerase II.
TATA-Binding Protein
TBP a general transcription factor that binds specifically to a DNA sequence called the TATA box
Transcription Factor II F
TFIIF a eukaryotic transcription factor often found associated with RNA polymerase II plays a role in the formation of the Pre-Initiation complex (PIC) prior to the initiation of gene transcription
Transcription Factor II Human
TFIIH an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways
Intiation, Elongation, Termination
Three Stages of Transcription
Basal Transcription Factors, Gene-Specific Transcription Factors
Two Groups of Transcription Factors
Lamins
a class of intermediate filament proteins that associate to form higher order structures Two interact to form a dimer: the α-helical regions wind around each other to form a coiled coil dimers associate with each other to form the Nuclear lamina bind to inner membrane proteins such as emerin and LBR connected to the cytoskeleton by LINC protein complexes also bind to chromatin
GC Box
a distinct pattern of nucleotides found in the promoter region of some eukaryotic genes upstream of the TATA box consensus sequence: GGGCGG commonly the binding site for Zinc finger proteins
CAAT Box
a distinct pattern of nucleotides with GGCCAATCT consensus sequence that occur upstream by 60-100 bases to the initial transcription site
Nucleolus
a distinct region where ribosomal RNA is synthesized and ribosome subunits are assembled
Nuclear Lamina
a fibrous mesh that provides structural support consists of fibrous proteins (lamins) and other proteins
Transcription Factor II B
a general transcription factor involved in the formation of the RNA polymerase II preinitiation complex aids in stimulating transcription initiation localised to the nucleus and provides a platform for PIC formation by binding and stabilising the DNA-TBP (TATA-binding protein) complex and by recruiting RNA polymerase II and other transcription factors
Fibrillin-1
a glycoprotein component of the extracellular matrix is a 230-kb gene with 65 coding exons that encode a 2,871-amino-acid long proprotein called profibrillin
Epidermolysis Bullosa
a group of rare diseases that cause fragile, blistering skin
Nuclear Transport Factor 2
a homodimer which stimulates efficient nuclear import of a cargo protein binds to RanGDP and FxFG containing nucleoporins folds into a cone with a deep hydrophobic cavity, the opening of which is surrounded by several negatively charged residues
Karyopherins
a nuclear transport receptor family composed of many importins and exportins
Mediator
a protein complex of more than 20 subunits; it interacts with both general transcription factors and RNA polymerase
Asprosin
a protein hormone produced by mammals in their fatty (white adipose) tissues that stimulates the liver to release glucose into the blood stream. In these tissues, it is encoded by the gene FBN1, which also encodes the protein fibrillin In the liver, it activates rapid glucose release via a cyclic adenosine monophosphate (cAMP) dependent pathway.
Nuclear Pore
a protein-lined channel in the nuclear envelope that regulates the transportation of molecules between the nucleus and the cytoplasm
Emerin
a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family mediates membrane anchorage to the cytoskeleton
Enhancer
a short (50-1500 bp) region of DNA that can be bound by proteins (activators) to increase the likelihood that transcription of a particular gene will occur
Junctional Epidermolysis Bullosa
a skin condition characterized by blister formation within the lamina lucida of the extra cellular matrix this type may be severe, with blisters beginning in infancy one type arises from mutations in the LAMA3 gene (laminin subunit alpha 3)
Corepressors
act by modifying chromatin structure
Nuclear Envelope
also known as the nuclear membrane is made up of two lipid bilayer membranes which surrounds the nucleus, and in eukaryotic cells it encases the genetic material studded with pore-like openings
Nuclear Localization Signals
amino acid sequences on proteins that must enter the nucleus
RNA Polymerase
an enzyme that binds to DNA during transcription and separates or unwinds the DNA strands
Transcriptional Activators
bind to regulatory DNA sequences and stimulate transcription Two independent domains: one region binds DNA, the other stimulates transcription by interacting with other proteins such as Mediator.
Zinc Finger Domain
binds zinc ions and folds into loops ("fingers") that bind DNA
Marfan Syndrome
caused by mutations in the FBN1 gene on chromosome 15
Proximal Control Elements
control elements located close to the start site
Ran
controls directionality of movement
Exportins
direct protein transport to the cytoplasm form stable complexes with cargo proteins in association with Ran/GTP in the nucleus
FBN1 Gene
encodes fibrillin-1
Transcription Factor II D
general transcription factor composed of multiple subunits, including the TATA-binding protein (TBP) and other subunits (TAFs) that bind to the Inr, DCE, MTE, and DPE sequences
Active Repressors
have domains that inhibit transcription via protein-protein interactions. These include interactions with specific activator proteins, with Mediator proteins or general transcription factors, and with corepressors
Steroid Hormone Receptors
have zinc fingers they regulate gene transcription in response to hormones such as estrogen and testosterone
Homeodomain Proteins
important in regulation of gene expression during embryonic development
Repressor
inhibit transcription by interfering with binding of other transcription factors or by competing with activators for binding to specific regulatory sequences
Emery-Dreifuss Muscular Dystrophy
is an X-linked inherited degenerative myopathy resulting from mutation in Emerin
Nucleus
large and highly organized surrounded by a double membrane
Nuclear Pore Complex
large; about 30 proteins (nucleoporins)
Profibrillin
long proprotein which is proteolytically cleaved near its C-terminus by the enzyme furin convertase to give fibrillin-1, a member of the fibrillin family, and the 140-amino-acid long protein hormone asprosin. Individuals have heterozygous, truncating mutations in the FBN1 gene1 and display a deficiency in circulating (plasma) asprosin most telling features of the condition are an aged appearance and extreme thinness. (lack of Asprosin)
Helix-Turn-Helix Domain
one helix makes most of the contacts with DNA, the others lie across the complex to stabilize the interaction
Transcription Factor II E
one of several general transcription factors that make up the RNA polymerase II preinitiation complex recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH
Polycomb Proteins
perform methylation of H3 Lysine 27 resulting in repression of regulatory genes in certain cells in developing Drosophila the repression is passed on in subsequent divisions
Nuclear Membrane
phospholipid bilayers permeable only to small nonpolar molecules
Core Promoter Elements
portion of the proximal promoter that contains the transcription start sites
Gene-Specific Transcription Factors
proteins that activate or repress basal transcription
Nuclear Transport Receptors
recognize nuclear localization signals
Importins
recognize nuclear localization signals carry proteins through the nuclear pore complex work in conjunction with the GTP-binding protein Ran bind to the NLS of a protein, then to nuclear pore proteins and the complex is transported across the membrane
Ran GDP
the dominant nucleotide binding state of Ran when it is located in the cytoplasm
Ran GTP
the dominant nucleotide binding state of Ran when it is located in the nucleus
RPB1
the largest subunit of RNA polymerase II It serves as a flexible binding scaffold for numerous nuclear factors, determined by the phosphorylation patterns on the CTD repeats
CTC-Binding Factor
the main protein that binds insulators in vertebrates
Epidermolysis Bullosa Simplex
the most common form of epidermolysis bullosa
Nuclear Pore Complexes
the only channels for small polar molecules ions and macromolecules
5' Untranslated Region
the region of an mRNA that is directly upstream from the initiation codon important for the regulation of translation of a transcript by differing mechanisms in viruses, prokaryotes and eukaryotes
3' Untranslated Region
the section of messenger RNA (mRNA) that immediately follows the translation termination codon
RNA Transcript
the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs are modified in preparation for translation
Dystrophic Epidermolysis Bullosa
this type is related to a flaw in the gene that helps produce a type of collagen
Karyopherin Exportins
transport tRNAs, rRNAs, miRNAs
Ran/GTP Importin Complex
transported back into the cytoplasm
Basal Transcription Factors
ubiquitous and recruit RNA polymerase II multi-protein complex to the minimal promoter
Nucleus
where does transcription occur
Cytoplasm
where does translation occur