GIO: L5 02-10 CONTROL OF GENE EXPRESSION

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33 Terms

1
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WHAT CONTAIN THE SAME GENOME?

  • DIFFERENT CELL TYPES!

  • GENE EXPRESSION IS THE PROCESS BY WHICH CELLS SELECTIVELY DIRECT THE SYNTHESIS OF SPECIFIC RNAS AND PROTEINS

  • DIFFERENTIATION IS THE PROCESS BY WHICH CELLS BECOME SPECIALIZED

  • DIFFERENT CELL TYPES EXPRESS DIFFERENT SETS OF GENES BUT CONTAIN THE SAME DNA

    • SPECIFIC RNAS AND PROTEINS DISTINGUISH CELL TYPES

    • “HOUSEKEEPER GENES” ARE EXPRESSED IN ALL CELL TYPES

<ul><li><p>DIFFERENT CELL TYPES!</p></li><li><p><strong>GENE EXPRESSIO</strong>N IS THE PROCESS BY WHICH CELLS SELECTIVELY DIRECT THE SYNTHESIS OF SPECIFIC RNAS AND PROTEINS</p></li><li><p><strong>DIFFERENTIATION</strong> IS THE PROCESS BY WHICH CELLS BECOME SPECIALIZED</p></li><li><p>DIFFERENT CELL TYPES EXPRESS DIFFERENT SETS OF GENES BUT CONTAIN THE SAME DNA</p><ul><li><p>SPECIFIC RNAS AND PROTEINS DISTINGUISH CELL TYPES</p></li><li><p>“HOUSEKEEPER GENES” ARE EXPRESSED IN ALL CELL TYPES</p></li></ul></li></ul><p></p>
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WHAT CAN BE REGULATED AT MULTIPLE STEPS?

  • GENE EXPRESSION!

  • TRANSCRIPTION IS REGULATED IN BOTH PROKARYOTES AND IN EUKARYOTES

<ul><li><p>GENE EXPRESSION!</p></li><li><p>TRANSCRIPTION IS REGULATED IN BOTH PROKARYOTES AND IN EUKARYOTES</p></li></ul><p></p>
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WHAT BIND TO DNA?

  • TRANSCRIPTION REGULATORS!

  • PROTEINS THAT REGULATE TRANSCRIPTION ARE CALLED TRANSCRIPTION FACTORS

  • TRANSCRIPION REGULATORS BIND TO SPECIFIC DNA SEQUENCES

  • WHEN TRANSCRIPTION REGULATORS BIND AS DIMERS, THE STRENGTH AND SPECIFICITY OF DNA-PROTEIN INTERACTION IS INCREASED

<ul><li><p>TRANSCRIPTION REGULATORS!</p></li><li><p>PROTEINS THAT REGULATE TRANSCRIPTION ARE CALLED TRANSCRIPTION FACTORS </p></li><li><p>TRANSCRIPION REGULATORS BIND TO SPECIFIC DNA SEQUENCES</p></li><li><p>WHEN TRANSCRIPTION REGULATORS BIND AS DIMERS, THE STRENGTH AND SPECIFICITY OF DNA-PROTEIN INTERACTION IS INCREASED</p></li></ul><p></p>
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WHAT ARE ARRANGED IN OPERONS?

  • PROKARYOTIC GENES

  • THE TRP (TRYPTOPHAN) OPERON IS AN EXAMPLE OF OPERONS

<ul><li><p>PROKARYOTIC GENES</p></li><li><p>THE TRP (TRYPTOPHAN) OPERON IS AN EXAMPLE OF OPERONS </p></li></ul><p></p>
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GENES CAN BE SWITCHED OFF BY…

  • REPRESSOR PROTEINS

  • THE LEVELS OF TRYPTOPHAN REGULATE THE EXPRESSION OF THE OPERON

  • THE TRP REPRESSOR IS A TRANSCRIPTIONAL REPRESSOR

<ul><li><p>REPRESSOR PROTEINS</p></li><li><p>THE LEVELS OF TRYPTOPHAN REGULATE THE EXPRESSION OF THE OPERON</p></li><li><p>THE TRP REPRESSOR IS A TRANSCRIPTIONAL REPRESSOR </p></li></ul><p></p>
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GENE EXPRESSION CAN BE SWITCHED ON BY…

  • ACTIVATOR PROTEINS

  • ACTIVATOR PROTEINS PROMOTE THE BINDING OF RNA POLYMERASE

  • REPRESSOR PROTEINS INTERFERE WITH THE BINDING OF RNA POLYMERASE

<ul><li><p>ACTIVATOR PROTEINS</p></li><li><p>ACTIVATOR PROTEINS PROMOTE THE BINDING OF RNA POLYMERASE</p></li><li><p>REPRESSOR PROTEINS INTERFERE WITH THE BINDING OF RNA POLYMERASE</p></li></ul><p></p>
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WHAT IS TRANSCRIPTIONAL REGULATION IN PROKARYOTES?

  • IN PROKARYOTES:

    • BOTH ACTIVATORS AND REPRESSORS REGULATE TRANSCRIPTION

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WHAT IS TRANSCRIPTIONAL REGULATION IN EUKARYOTES?

  • IN EUKARYOTES

  • PROMOTER ACCESS IS RESTRICTED

    • CONDENSED CHROMATIN IS INACCESSIBLE

    • CHROMATIN MUST BE REMODELED

    • TRANSCRIPTION REGULATORS CAN RECRUIT CHROMATIN-REMODELING PROTEINS TO ACTIVATE TRANSCRIPTION

  • ACTIVATION CAN OCCUR AT A DISTANCE

    • ENHANCERS RECRUIT CHROMATIN-REMODELING ENZYMES

    • ENHANCERS RECRUIT TRANSCRIPTIONAL ACTIVATORS

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WHAT CAN BE CONTROLLED AT A DISTANCE?

  • EUKARYOTIC GENE ACTIVATION!

  • EUKARYOTIC TRANSCRIPTIONAL REGULATORS BIND ENHANCERS (A DNA SEQUENCE)

  • THE MEDIATOR COMPLEX LINKS ACTIVATORS AND THE GENERAL TRANSCRIPTION MACHINERY TO PROMOTE (OR REPRESS) ASSEMBLY

<ul><li><p>EUKARYOTIC GENE ACTIVATION!</p></li><li><p>EUKARYOTIC TRANSCRIPTIONAL REGULATORS BIND <strong>ENHANCERS</strong> (A DNA SEQUENCE)</p></li><li><p>THE <strong>MEDIATOR COMPLEX</strong> LINKS ACTIVATORS AND THE GENERAL TRANSCRIPTION MACHINERY TO PROMOTE (OR REPRESS) ASSEMBLY </p></li></ul><p></p>
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WHAT MEDIATE ENHANCER-PROMOTOR INTERACTIONS?

  • DNA LOOPS!

<ul><li><p>DNA LOOPS!</p></li></ul><p></p>
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EUKARYOTIC GENE TRANSCRIPTION REGULATORS CAN…

  • RECRUIT CHROMATIN MODIFYING PROTEINS!

  • HISTONE ACETYLTRANSFEREASES ADD (WRITERS) ACETYL GROUPS TO HISTONE TAILS “LOOSENING” THE CHROMATIN

  • HISTONE DEACETYLASES REMOVE (ERASERS) ACETYL MODIFICATIONS FROM HISTONES

  • ATP-DEPENDENT CHROMATIN REMODELING COMPLEXES REPOSITION DNA ON NUCLEOSOMES

<ul><li><p>RECRUIT CHROMATIN MODIFYING PROTEINS!</p></li><li><p>HISTONE ACETYLTRANSFEREASES ADD (WRITERS) ACETYL GROUPS TO HISTONE TAILS “LOOSENING” THE CHROMATIN</p></li><li><p>HISTONE DEACETYLASES REMOVE (ERASERS) ACETYL MODIFICATIONS FROM HISTONES</p></li><li><p>ATP-DEPENDENT CHROMATIN REMODELING COMPLEXES REPOSITION DNA ON NUCLEOSOMES</p></li></ul><p></p>
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WHAT IS COMBINATORIAL CONTROL OF TRANSCRIPTION?

  • MANY EUKARYOTIC GENES ARE UNDER COMBINATORIAL CONTROL BY MULTIPLE TRANSCRIPTION REGULATORS

  • TOGETHER, THESE REGULATORS DETERMINE THE RATE OF TRANSCRIPTION

<ul><li><p>MANY EUKARYOTIC GENES ARE UNDER COMBINATORIAL CONTROL BY MULTIPLE TRANSCRIPTION REGULATORS </p></li><li><p>TOGETHER, THESE REGULATORS DETERMINE THE RATE OF TRANSCRIPTION </p></li></ul><p></p>
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WHAT IS COMBINATORIAL CONTROL OF TRANSCRIPTION: THE EXAMPLE OF EVE?

  • MULTIPLE TRANSCRIPTIONAL REGULATORS (PROTEINS) BIND REGULATORY SEQUENCES

  • MULTIPLE REGULATORY SEGMENTS (DNA) DETERMINE EXPRESSION PATTERNS

<ul><li><p>MULTIPLE TRANSCRIPTIONAL REGULATORS (PROTEINS) BIND REGULATORY SEQUENCES </p></li><li><p>MULTIPLE REGULATORY SEGMENTS (DNA) DETERMINE EXPRESSION PATTERNS </p></li></ul><p></p>
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WHAT CAN COORDINATE EXPRESSION OF MANY GENES?

  • A SINGLE TRANSCRIPTIONAL REGULATOR!

  • EXAMPLE: CORTISOL RECEPTOR

    • CORTISOL RECEPTOR US A TRANSCRIPTIONAL REGULATOR

    • MANY COPIES OF THE CORTISOL RECEPTOR ARE PRESENT IN A SINGLE LIVER CELL

    • MANY GENES CONTAIN THE SAME CORTISOL RECEPTOR REGULATORY SEQUENCE

    • IN THE PRESENCE OF CORTISOL, THE CORTISOL RECEPTOR BINDS TO THE DNA AND INTERACTS WITH TRANSCRIPTIONAL ACTIVATORS TO PROMOTE HIGH LEVELS OF TRANSCRIPTION

<ul><li><p>A SINGLE TRANSCRIPTIONAL REGULATOR!</p></li><li><p>EXAMPLE: CORTISOL RECEPTOR</p><ul><li><p>CORTISOL RECEPTOR US A TRANSCRIPTIONAL REGULATOR </p></li><li><p>MANY COPIES OF THE CORTISOL RECEPTOR ARE PRESENT IN A SINGLE LIVER CELL</p></li><li><p>MANY GENES CONTAIN THE SAME CORTISOL RECEPTOR REGULATORY SEQUENCE</p></li><li><p>IN THE PRESENCE OF CORTISOL, THE CORTISOL RECEPTOR BINDS TO THE DNA AND INTERACTS WITH TRANSCRIPTIONAL ACTIVATORS TO PROMOTE HIGH LEVELS OF TRANSCRIPTION </p></li></ul></li></ul><p></p>
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DIFFERENT COMBINATIONS OF TRANSCRIPTIONAL REGULATORS CAN…

  • GENERATE DIFFERENT CELL TYPES!

  • HYPOTHETICAL SCHEME: 7 DIFFERENT CELL TYPES ARE GENERATED USING 3 DIFFERENT TRANSCRIPTIONAL REGULATORS

<ul><li><p>GENERATE DIFFERENT CELL TYPES!</p></li><li><p>HYPOTHETICAL SCHEME: 7 DIFFERENT CELL TYPES ARE GENERATED USING 3 DIFFERENT TRANSCRIPTIONAL REGULATORS</p></li></ul><p></p>
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WHAT IS CELLULAR PROGRAMMING?

  • DIFFERENTIATED CELLS CONTAIN ALL THE GENETIC INSTRUCTIONS NEEDED TO DIRECT THE FORMATION OF A COMPLETE ORGANISM

<ul><li><p>DIFFERENTIATED CELLS CONTAIN ALL THE GENETIC INSTRUCTIONS NEEDED TO DIRECT THE FORMATION OF A COMPLETE ORGANISM </p></li></ul><p></p>
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WHAT IS CELLULAR REPROGRAMMING?

  • DIFFERENTIATED CELLS CAN BE CONVERTED FROM ONE CELL TYPE TO ANOTHER BY EXPRESSING SPECIFIC TRANSCRIPTIONAL REGULATORS

  • DIFFERENTIATED CELLS CAN BE CONVERTED TO PLURIPOTENT STEM CELLS EXPRESSING SPECIFIC TRANSCRIPTIONAL FACTORS

<ul><li><p>DIFFERENTIATED CELLS CAN BE CONVERTED FROM ONE CELL TYPE TO ANOTHER BY EXPRESSING SPECIFIC TRANSCRIPTIONAL REGULATORS</p></li><li><p>DIFFERENTIATED CELLS CAN BE CONVERTED TO PLURIPOTENT STEM CELLS EXPRESSING SPECIFIC TRANSCRIPTIONAL FACTORS </p></li></ul><p></p>
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WHAT ARE THE MULTIPLE STEPS THAT GENE EXPRESSION CAN BE REGULATED AT?

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WHAT IS THE FUNCTION OF MESSENGER RNAS (MRNAS)?

CODE FOR PROTEINS

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WHAT IS THE FUNCTION OF RIBOSOMAL RNAS (RRNAS)?

FORM THE CORE OF THE RIBOSOME’S STRUCTURE AND CATALYZE PROTEIN SYNTHESIS

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WHAT IS THE FUNCTION OF MICRORNAS (MIRNAS)?

REGULATE GENE EXPRESSION

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WHAT IS THE FUNCTION OF TRANSFER RNAS?

SERVE AS ADAPTORS BETWEEN MRNA AND AMINO ACIDS DURING PROTEIN SYNTHESIS

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WHAT IS THE FUNCTION OF SMALL INTERFERING RNAS (SIRNAS)?

PROVIDE PROTECTION FROM VIRUSES AND PROLIFERATING TRANSPOSABLE ELEMENTS

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WHAT IS THE FUNCTION OF LONG NONCODING RNAS (LNCRNAS)?

ACT AS SCAFFOLDS AND SERVE OTHER DIVERSE FUNCTIONS, MANY OF WHICH ARE STILL BEING DISCOVERED

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WHAT IS THE FUNCTION OF OTHER NONCODING RNAS?

USED IN RNA SPLICING, GENE REGULATION, TELOMERE MAINTENANCE, AND MANY OTHER PROCESSES

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WHAT TARGET RNAS FOR DEGRADATION?

  • MICRORNAS (MIRNAS) CONTROL GENE EXPRESSION THROUGH BASE-PAIRING INTERACTIONS

  • MATURE MIRNAS ARE -22 NTS IN LENGTH

  • SINGLE-STRANDED MIRNAS FORM A COMPLEX WITH PROTEINS TO FORM A RNA-INDUCED SILENCING COMPLEX (RISC)

  • RISC BINDS TO COMPLEMENTARY RNA SEQUENCES

  • RESULT: DEGRADATION OF THE TARGET MRNA

<ul><li><p>MICRORNAS (MIRNAS) CONTROL GENE EXPRESSION THROUGH BASE-PAIRING INTERACTIONS</p></li><li><p>MATURE MIRNAS ARE -22 NTS IN LENGTH</p></li><li><p>SINGLE-STRANDED MIRNAS FORM A COMPLEX WITH PROTEINS TO FORM A RNA-INDUCED SILENCING COMPLEX (RISC)</p></li><li><p>RISC BINDS TO COMPLEMENTARY RNA SEQUENCES </p></li><li><p>RESULT: DEGRADATION OF THE TARGET MRNA</p></li></ul><p></p>
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WHAT IS GENE SILENCING BY RNA INTERFERENCE?

  • SMALL INTERFERING RNAS (SIRNAS) ARE PRODUCED FROM DOUBLE-STRANDED FOREIGN RNAS

  • DICER IS AN ENDONUCLEASE THAT CLEAVES FOREIGN DOUBLE-STRANDED RNAS

  • SINGLE-STRANDED SIRNAS FORM A COMPLEX WITH PROTEINS TO FORM AN RNA-INDUCED SILENCING COMPLEX (RISC)

  • RISC BINDS TO COMPLEMENTARY RNA SEQUENCES

  • RESULT: DEGRADATION OF THE TARGET MRNA

<ul><li><p>SMALL INTERFERING RNAS (SIRNAS) ARE PRODUCED FROM DOUBLE-STRANDED FOREIGN RNAS</p></li><li><p>DICER IS AN ENDONUCLEASE THAT CLEAVES FOREIGN DOUBLE-STRANDED RNAS</p></li><li><p>SINGLE-STRANDED SIRNAS FORM A COMPLEX WITH PROTEINS TO FORM AN RNA-INDUCED SILENCING COMPLEX (RISC)</p></li><li><p>RISC BINDS TO COMPLEMENTARY RNA SEQUENCES </p></li><li><p>RESULT: DEGRADATION OF THE TARGET MRNA</p></li></ul><p></p>
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WHO DISCOVERED RNA INTERFERENCE?

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WHO DISCOVERED MICRORNAS?

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WHAT ARE CAENORHABDITIS ELEGANS?

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WHAT IS POST-TRANSLATIONAL MODIFICATION OF PROTEINS?

POST-TRANSLATIONAL MODIFICATIONS INCLUDE:

1) METHYLATION

2) ACETYLATION

3) PHOSPHORYLATION

4)UBIQUITINATION

5)GLYCOSYLATION

MODIFICATIONS CAN AFFECT BINDING TO CO-FACTORS, STABILITY, AND SUBCELLULAR LOCALIZATION

<p>POST-TRANSLATIONAL MODIFICATIONS INCLUDE:</p><p>1) METHYLATION</p><p>2) ACETYLATION</p><p>3) PHOSPHORYLATION </p><p>4)UBIQUITINATION</p><p>5)GLYCOSYLATION</p><p></p><p>MODIFICATIONS CAN AFFECT BINDING TO CO-FACTORS, STABILITY, AND SUBCELLULAR LOCALIZATION</p>
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WHAT IS REGULATION OF PROTEIN DEGRADATION?

  • PROTEOLYSIS: THE BREAKDOWN OF PROTEINS INTO THEIR CONSTITUENT AMINO ACIDS

  • PROTEASES: CUT PEPTIDE BONDS

  • PROTEASOME: A MULTI-SUBUNIT MACHINE THAT DEGRADES PROTEINS

  • PROTEINS TO BE DEGRADED ARE MARKED BY THE COVALENT ADDITION OF UBIQUITIN

<ul><li><p>PROTEOLYSIS: THE BREAKDOWN OF PROTEINS INTO THEIR CONSTITUENT AMINO ACIDS</p></li><li><p>PROTEASES: CUT PEPTIDE BONDS</p></li><li><p>PROTEASOME: A MULTI-SUBUNIT MACHINE THAT DEGRADES PROTEINS </p></li><li><p>PROTEINS TO BE DEGRADED ARE MARKED BY THE COVALENT ADDITION OF UBIQUITIN </p></li></ul><p></p>
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WHAT ARE THE 3 STEPS THAT GENE EXPRESSION CAN BE REGULATED?

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