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